Heat ablation systems, devices and methods for the treatment of tissue

ABSTRACT

A system for treatment target tissue comprises an ablation device and an energy delivery unit. The ablation device comprises an elongate tube with an expandable treatment element. The system delivers a thermal dose of energy to treat the target tissue. Methods of treating target tissue are also provided.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/470,503, filed Aug. 27, 2014, now U.S. Pat. No. 10,349,998, which isa continuation of International Patent Application No.PCT/US2013/028082, filed Feb. 27, 2013, which claims priority from U.S.Provisional Application No. 61/603,475, filed Feb. 27, 2012, the entirecontents of which are incorporated herein by reference.

This application is related to PCT/US2012/021739, entitled Devices andMethods for the Treatment of Tissue, filed on Jan. 18, 2012, whichclaimed the benefit of U.S. Provisional Application Ser. No. 61/434,319,entitled Method and System for Treatment of Diabetes, filed Jan. 19,2011, and of U.S. Provisional Application Ser. No. 61/538,601, entitledDevices and Methods for the Treatment of Tissue, filed Sep. 23, 2011,the contents of which are each incorporated herein by reference in theirentirety.

TECHNICAL FIELD

The embodiments disclosed herein relate generally to systems, devicesand methods for treating tissue, particularly gastrointestinal tissue.

BACKGROUND

Diabetes is a metabolic disease in which a person develops high bloodsugar because the person's body does not produce enough insulin or thecells of the body are incapable of effectively responding to theproduced insulin. Primarily, diabetes is of two types: Type-1 andType-2. Type-1 diabetes results from to the body's failure to produceenough insulin, due to the body's autoimmune destruction of pancreaticbeta cells. Type-2 diabetes, on the other hand, is a complex metabolicderangement that causes hyperglycemia through insulin resistance (inwhich the body's cells fail to properly utilize the produced insulin)and inadequate insulin production to meet the body's needs.

Currently, there are several procedures aimed at treating diabetes basedon the above concept. The procedures require major surgery, removal ofportions of the GI tract, and/or long-term implants. As with any majorsurgery, gastric bypass surgery carries a risk of complications.

Devices have been developed to delivery energy to the body. For example,cardiac ablation devices have been designed to delivery ablative energyto coronary tissue. Additionally, urethral resection devices have beendesigned to burn or cut away portions of a prostate. Each of thesetechnologies has been modified and adapted toward effective usage in theparticular portion of the body to be treated as well as the particulardisease to be treated.

There is a need for systems and methods that can provide a therapeutictreatment of the GI tract by the application of energy to the GI tract.Specifically, there is a need to provide a treatment of diabetes with aprocedure in the GI tract that is less invasive than gastric bypasssurgery and has other advantages for patients.

SUMMARY

According to one aspect of the inventive concepts, a system for treatingtarget tissue comprises an ablation device and an energy delivery unit.The ablation device comprises an elongate tube with a proximal portion,a distal portion, and a lumen extending from the proximal portion to thedistal portion. The ablation device further comprises an expandabletreatment element mounted to the elongate tube and in fluidcommunication with the lumen. The energy delivery unit is constructedand arranged to deliver energy to the treatment element. The system isconstructed and arranged to deliver a thermal dose of energy to thetarget tissue.

The thermal dose may be determined prior to and/or during the treatmentof the target tissue. The thermal dose may be based on one or moreparameters, such as one or more parameters selected from the groupconsisting of: heat transfer properties of the treatment elementmaterial; heat transfer properties of the target tissue; heat transfercoefficient at the interface between the treatment element and thetarget tissue; and combinations thereof.

The system may comprise an algorithm wherein the thermal dose isdetermined by the algorithm. The algorithm may include a model of thetransfer of heat into the target tissue. The algorithm may account fortissue perfusion in or proximate to the target tissue. The algorithm maybe based on patient measured data, such as data gathered during theperformance of a calibration routine integral to the system. Thealgorithm may be based on data from a large number of human and/or othermammalian subjects.

The thermal dose may comprise energy delivered by a single bolus ofheated fluid that is delivered to the treatment element. The singlebolus may comprise a fixed mass of heated fluid, and the single bolusmay be maintained at a particular pressure or range of pressures. Thesingle bolus pressure or pressure range may be selected to provide afunction selected from the group consisting of: maintaining a thermalprofile; expanding the treatment element to a desired diameter;expanding the target tissue to a desired diameter; distending the targettissue; compressing a layer of the target tissue such as a mucosallayer; and combinations of these. The single bolus may comprise a singlebolus mass that is based on the pressure and/or diameter of thetreatment element.

The thermal dose may comprise a series of single bolus heated fluiddeliveries. Alternatively or additionally, the thermal dose may comprisecirculating heated fluid delivered into and out of the treatmentelement. The continuously delivered heated fluid may be maintained at arelatively constant temperature and/or at varied temperatures. In someembodiments, the delivered fluid is maintained at temperatures between65° C. and 99° C. In some embodiments, fluid is delivered at a firsttemperature for a first time period and/or for a first volume, and fluidis delivered at a different, second temperature for a second time periodand/or a second volume. The delivered, heated fluid may be abiocompatible fluid. The delivered, heated fluid may comprise a liquid,gas or gel, such as a fluid selected from the group consisting of:water; saline; perfluorinated compounds; and combinations of these.

The thermal dose may comprise a fixed duration of energy delivery.Alternatively or additionally, the thermal dose may comprise acontinuously time-varying delivery of energy. The continuouslytime-varying delivery of energy may be provided by recirculating hotfluid through the treatment element. A heating element may be includedto heat the circulating fluid, such as a heating element positioned inand/or proximate to the treatment element. The continuously time-varyingdelivery of energy may comprise periodic thermal dilution of fluid inthe treatment element, such as when the system includes a first sourceof fluid and a second source of fluid, and the first source of fluidprovides fluid at a temperature different than the second source offluid.

The thermal dose may comprise a delivery of energy comprising aquasi-steady-state temperature profile. In these embodiments, thethermal dose may comprise energy delivered by a fluid maintained between45° C. and 50° C. In these embodiments, the fluid may be recirculated inthe treatment element. The system may be configured to monitor progressof target tissue ablation by monitoring time rate of energy transferinto the treatment element.

The thermal dose may comprise an energy delivered based on time-averagedtemperature control over a time period.

The thermal dose may comprise energy delivered at a relatively constanttemperature. In some embodiments, the thermal dose comprises energydelivered from a fluid at a temperature between 65° C. and 99° C. Insome embodiments, the thermal dose comprises energy delivered from afluid at a temperature of approximately 65° C. for a duration ofapproximately 30 seconds to 60 seconds. In some embodiments, the thermaldose comprises energy delivered from a fluid at a temperature ofapproximately 70° C. for a duration of approximately 5 seconds to 45seconds. In some embodiments, the thermal dose comprises energydelivered from a fluid at a temperature of approximately 75° C. for aduration of approximately 3 seconds to 40 seconds. In some embodiments,the thermal dose comprises energy delivered from a fluid at atemperature of approximately 80° C. for a duration of approximately 3seconds to 30 seconds. In some embodiments, the thermal dose comprisesenergy delivered from a fluid at a temperature of approximately 90° C.for a duration of approximately 3 seconds to 20 seconds.

The system may be constructed and arranged to deliver multiple thermaldoses of energy to the target tissue. A first dose may be delivered to afirst tissue location and a second dose delivered to a second tissuelocation. A first dose may be delivered at a first temperature and asecond dose delivered at a temperature similar or dissimilar to thefirst dose temperature. In some embodiments, the second dose temperatureis incrementally greater than the first dose temperature. A first dosemay be applied for a first time period and the second dose may beapplied for a second time period, where the first and second timeperiods are of similar or dissimilar lengths of time. The system may beconstructed and arranged to modify one or more parameters between afirst thermal dose delivery and a second thermal dose delivery, such asone or more parameters selected from the group consisting of:temperature; time duration; and combinations of these.

The system may be constructed and arranged to measure one or moreablation parameters and adjust the thermal dose based on thismeasurement. The measured ablation parameter may be a parameter selectedfrom the group consisting of: temperature decay of the temperature in,on and/or near the treatment element; temperature of the target tissue;temperature of tissue proximate the target tissue; temperature ofnon-target tissue; temperature of fluid in the treatment element; andcombinations of these. The system may be configured to stop delivery ofenergy based on the measurement. The system may be configured to performa calibration procedure, such as to model temperature decay.

The system may be constructed and arranged to perform a calibrationroutine. The calibration routine may include the delivery of acalibration bolus. The calibration routine may comprise delivery offluid to the treatment element, such as fluid delivered at a temperaturebelow a level that would cause tissue ablation, such as a temperaturebelow 41° C. The system may comprise an algorithm based on informationgathered during the calibration routine, such as an algorithm used todetermine one or more thermal dose parameters. The thermal doseparameters may comprise one or more parameters selected from the groupconsisting of: temperature of thermal dose; temperature profile ofthermal dose; duration of thermal dose; pressure applied during thermaldose; and combinations of these.

The system may be constructed and arranged to monitor residual heatpresent in the target tissue. The residual heat may be measured betweena first delivery of energy and a second delivery of energy. The systemmay include a sensor, such as at least one sensor positioned on thetreatment element. Signals from the at least one sensor may be used tomeasure residual heat.

The system may include an inflow port and an outflow port, such as aninflow port and/or an outflow port fluidly attached to one or morelumens of the ablation device. In some embodiments, the inflow port ismaintained at a first pressure while the outflow port is maintained at asecond pressure, less than the first pressure. In some embodiments, theinflow port is attached to a fluid delivery source (e.g. a source offluid at a positive pressure) and the outflow port is attached to anegative pressure source.

The system may comprise a rapid thermal response time, such as aresponse time to inflate a treatment element and achieve a targettemperature and/or a response time for a treatment element to achieve amodified target temperature. In some embodiments, the rapid thermalresponse time includes a thermal dose reaching 90% of a desired,modified target temperature within fifteen seconds of initiating achange to the modified target temperature. In some embodiments, therapid thermal response time includes a rise in thermal dose temperatureto 90% of a desired target temperature that occurs within five secondsof initiating the inflation of the treatment element.

The thermal dose may be constructed and arranged to ablate duodenalmucosa while avoiding damage to the duodenal muscularis propria orserosa. The thermal dose may be constructed and arranged to ablate oneor more inner layers of tissue of a hollow organ while avoiding damageto one or more outer layers of a hollow organ. The thermal dose may beconstructed and arranged to ablate target tissue while avoiding damageto non-target tissue.

The system may be constructed and arranged to increase the temperatureof fluid in the treatment element prior to expanding the treatmentelement to contact the target tissue.

The treatment element may comprise a balloon. The balloon may comprise acompliant balloon or a non-compliant balloon. The treatment element maycomprise multiple balloons, such as multiple individually expandableballoons and/or multiple balloons that can be individually filled withfluid.

The treatment element may comprise a balloon with multiple chambers. Insome embodiments, an outer chamber at least partially surrounds an innerchamber. The inner chamber and/or the outer chamber may be filled withhot fluid configured to deliver the thermal dose. In some embodiments,the outer chamber is filled with hot fluid and the inner chamber isfilled with other fluid used to radially expand the treatment element.

The treatment element may be constructed and arranged to initiallyexpand after pressure applied internally exceeds a threshold pressure.This pressure-thresholded treatment element may be pre-heated bydelivering hot fluid at a pressure below this threshold pressure, suchas when the treatment element is fluidly attached to an inflow port andan outflow port of the ablation device, and the inflow port ismaintained at a pressure above the outflow port pressure but below thetreatment element threshold pressure. The inflow port pressure may beabove room pressure while the outflow port pressure is below roompressure. The expandable treatment element may be configured such thatpressurization above the threshold pressure causes the rate of heattransfer from the treatment element to target tissue to be increased,such as an increase caused by the walls of the treatment elementthinning and/or the apposition between the treatment element and thetarget tissue increasing.

The system may be constructed and arranged to thermally prime theexpandable treatment element. The thermal priming may comprisedelivering heated fluid at a pressure below a pressure that would causethe treatment element to fully or partially expand. The ablation devicemay include an inlet port used to supply the thermal priming fluid. Theablation device may include an outlet port used to evacuate the thermalpriming fluid.

The system may be constructed and arranged to rapidly inflate theexpandable treatment element, such as to inflate the treatment elementwithin ten seconds. The system may be constructed and arranged torapidly deflate the treatment element, such as to deflate the treatmentelement within ten seconds.

The system may be constructed and arranged to move the target tissueaway from the treatment element to stop delivery of the thermal dose tothe target tissue, such as within a time period of no more than tenseconds from initiation of the target tissue movement. The tissuemovement may be caused by insufflation fluid delivered by the system.Alternatively or additionally, the tissue movement may be caused by atissue manipulator assembly of the system, such as a tissue manipulatorcomprising an expandable cage and/or a balloon.

The system may be constructed and arranged to move the target tissuetoward the treatment element to initiate delivery of energy to thetarget tissue, such as within a time period of no more than ten secondsfrom initiation of target tissue movement. The tissue movement may becaused by removing fluid in proximity to the target tissue, such as byapplying negative pressure through a lumen and/or exit port of thesystem, such as through the lumen or exit port of an endoscope.

The system may comprise an energy transfer modifying element constructedand arranged to improve the transfer of energy between the expandabletreatment element and the target tissue. The energy transfer modifyingelement may comprise a coating, such as a coating selected from thegroup consisting of: a metal coating; a hydrogel; and combinations ofthese. In some embodiments, the expandable treatment element comprises awall and the energy transfer modifying element is positioned within atleast a portion of the wall. The energy transfer modifying element maycomprise an element selected from the group consisting of: a wire mesh;a surface texture; one or more surface projections such as one or moreprojections that interdigitate with tissue; and combinations of these.

The expandable treatment element may comprise at least a portion whichis permeable, such as a permeable membrane portion. The permeableportion may be constructed and arranged to deliver fluid to targettissue, such as by delivering heated, biocompatible fluid to targettissue.

The elongate tube of the ablation device may comprise multiple lumens,such as a second lumen also in fluid communication with the expandabletreatment element such that fluid can be delivered into the expandabletreatment element via the first lumen and extracted from the expandabletreatment element via the second lumen. Pressure regulation within thefirst and second lumens, such as via ports connected to these lumens,can be used to aggressively inflate and/or deflate the expandabletreatment element. Pressure regulation can also be used to preciselycontrol flow through the expandable treatment element.

The system may include a second elongate tube, such as a second elongatetube of the ablation device. The second elongate tube may include aproximal portion, a distal portion and a lumen extending from theproximal portion to the distal portion. The second elongate tube may bepositioned within the first elongate tube, such as to be slidinglyreceived by the first elongate tube. Alternatively, the second elongatetube may be positioned in a side-by-side configuration with the firstelongate tube. The first elongate tube and/or the second elongate tubemay be configured to be advanced or retracted, such as to deliver a flowpattern delivered by the first and/or second elongate tube into thetreatment element. The second elongate tube may include a portconfigured to extract fluid from the treatment element (e.g. fluiddelivered by the first elongate tube), and the extraction port may bepositioned or positionable proximal to the treatment element, such as tocause desired flow dynamics within the treatment element, such as duringa thermal priming procedure or delivery of a thermal dose.

The system may comprise one or more radial support structures, such asone or more radial support structures positioned within the ablationdevice to prevent collapse of the elongate tube; the lumen of theablation device; and/or the treatment element. Radial collapse may needto be prevented during high flow fluid extraction events, such as duringa thermal priming procedure and/or evacuation of a thermal dose fluidfrom the treatment element.

The system may comprise one or more valves, such as a valve constructedand arranged to be opened to evacuate fluid from the treatment element.The valve may be positioned within the treatment element or within oneor more lumens of the elongate tube, such as when a first lumen is usedto fill the treatment element with fluid and a second lumen is used toevacuate fluid from the treatment element.

The system may comprise a positioning assembly constructed and arrangedto position the expandable treatment element relative to tissue. Thepositioning assembly may include an expandable cage and a deploymentshaft. A floating tube may be connected to the expandable cage andslidingly received by the ablation device such as to be retracted byretraction of the deployment shaft. The positioning assembly maycomprise a radially expandable element, such as a balloon or a cage,and/or a radially extendable element such as a radially deployable arm.The positioning assembly may be constructed and arranged to position thetreatment element within tubular tissue, such as to position thetreatment element at the geometric center of a lumen or off-center inthe lumen. The positioning assembly may be configured to position thetreatment element away from tissue and/or in contact with tissue. Thepositioning assembly may comprise one or more deployment shaftsconfigured to expand or extend one or more elements of the positioningassembly. The positioning assembly may be positioned proximal to thetreatment element, distal to the treatment element, at the samelongitudinal position as the treatment element, or combinations ofthese. The positioning assembly may be configured to move the treatmentelement away from tissue, such as a movement than occurs within fiveseconds or within 1 second.

The system may include an energy delivery unit, such as a syringe orother vessel containing heated fluid. The energy delivery unit mayinclude one or more fluid heaters, such as a fluid heater positioned ina location selected from the group consisting of: within the elongatetube; within the treatment element; external to the ablation device; andcombinations of these. The energy delivery unit may include a fluidpump, such as a pump that delivers and/or removes fluid to and/or fromthe treatment element. The energy delivery unit may provide fluid atmultiple temperatures, such as a volume of fluid at a first temperatureand a volume of fluid at a second temperature. The second volume offluid may be used to change (e.g. increase or decrease) the temperatureof the first volume of fluid, such as to dilute the first volume offluid after its delivery to the treatment element.

The system may include a sensor, such as one or more sensors configuredto modify an energy delivery parameter. The energy delivery parametermodified may include one or more of: energy level; power; andtemperature. The sensor may include one or more sensors selected fromthe group consisting of: thermocouple; thermistor; resistancetemperature detector (RTD); optical pyrometer; fluorometer; andcombinations of these. The sensor may comprise one or more sensorsconstructed and arranged to measure a parameter selected from the groupconsisting of: pressure such as fluid pressure; flow rate; temperaturesuch as a fluid temperature; viscosity; density; optical clarity;impedance such as tissue impedance; and combinations of these.Alternatively or additionally, the sensor may comprise one or moresensors constructed and arranged to measure a parameter selected fromthe group consisting of: tissue impedance such as electrical impedanceand thermal impedance; tissue color; tissue clarity; tissue compliance;tissue fluorescence; and combinations of these.

In some embodiments, the sensor comprises a force sensor constructed andarranged to measure the physical contact between the expandabletreatment element and the target tissue. In some embodiments, the sensorcomprises a strain gauge positioned on the expandable treatment element.In some embodiments, the sensor is positioned on the ablation devicesuch as to make contact with tissue, such as target tissue. The tissuecontacting sensor may comprise a pressure and/or temperature sensor. Thetissue contacting sensor may be positioned within a wall and/or on anexternal surface of the treatment element.

In some embodiments, the sensor comprises two or more temperaturesensors, wherein at least one sensor is mounted to the expandabletreatment element.

The system may comprise a controller constructed and arranged to modifydelivery of the thermal dose, such as by modifying one or more of:energy delivery; temperature of a fluid delivered to the expandabletreatment element; flow rate of a fluid delivered to the expandabletreatment element; pressure of a fluid delivered to the expandabletreatment element; and combinations of these. The controller may modifytemperature, flow rate and/or pressure based on a parameter selectedfrom the group consisting of: one or more measured properties of adelivered fluid; one or more measured properties of the expandabletreatment element; one or more measured properties of the target tissue;and combinations of these.

The system may include a temperature adjusting assembly, such as anassembly comprising a first supply of fluid delivered to the expandabletreatment element and a second supply of fluid delivered to theexpandable treatment element. The second supply of fluid may be mixedwith the first supply of fluid in the treatment element and/or at alocation proximal to the first treatment element. The second supply offluid may be configured to cool the first supply of fluid, such as acooling performed within the treatment element.

The system may include a fluid mixing assembly constructed and arrangedto cause fluid mixing within the expandable treatment element. The fluidmixing assembly may include at least one nozzle and/or at least one flowdirector. The fluid mixing assembly may comprise a fluid delivery tubecomprising a distal delivery port and a fluid extraction tube comprisinga distal extraction port. The delivery port and the extraction port maybe positioned to cause fluid mixing within the expandable treatmentelement. The fluid delivery tube and the fluid extraction tube may beco-luminal, such as when the fluid delivery tube is positioned withinthe fluid extraction tube. Alternatively, the fluid delivery tube andthe fluid extraction fluid may be positioned in a side-by-sidearrangement.

The system may include a negative pressure priming assembly. Theablation may comprise a fluid pathway and the negative pressure primingassembly may be configured to remove fluid from this fluid pathway. Thenegative pressure priming assembly is constructed and arranged toimprove the thermal rise time of the system.

The system may include a motion transfer element constructed andarranged to longitudinally position the expandable treatment element. Insome embodiments, the target tissue comprises a first tissue portion anda second tissue portion, and the motion transfer element is configuredto position the treatment element to treat the first tissue portion in afirst energy delivery and to treat the second tissue portion and asubportion of the first tissue portion in a second energy delivery. Thetarget tissue may comprise a third tissue portion and the motiontransfer element may be configured to treat the third tissue portion anda subportion of the second tissue portion in a third energy delivery.The first tissue portion and the second tissue subportion may beapproximately equal in length, such as when the overlap in tissuetreated between treatments is approximately the same.

The target tissue treated may comprise duodenal tissue. The duodenaltissue treated may be selected from the group consisting of: at least afull length of duodenal tissue; at least a full circumference ofduodenal tissue; a full mucosal layer of duodenal tissue; andcombinations of these.

The system of the present inventive concepts may comprise multipletreatment elements, such as a comprising a second treatment element. Insome embodiments, the ablation device includes the second treatmentelement. In other embodiments, the second treatment element is integralto a separate device, such as a second ablation device.

According to another aspect of the inventive concepts, a method fortreating target tissue comprises providing an ablation device anddelivering a thermal dose to target tissue. The ablation devicecomprises an expandable treatment element, and the thermal dosecomprises delivering energy from the expandable treatment element to thetarget tissue. The thermal dose comprises one or more of: an amount ofenergy determined by adjusting the apposition between the treatmentelement and the target tissue; a thermal dose initiated by reducing thediameter of target tissue to contact the treatment element; an amount ofenergy delivered by a single bolus of fluid; an amount of energydelivered by a fluid maintained at a pre-determined temperature for aduration of time; an amount of energy delivered by a fluid maintained ata pre-determined temperature for a pre-determined duration of time; anda thermal dose delivered after a priming procedure has been performed.

The method may further comprise the selection of target tissue to betreated, such as multiple target tissue portion treated sequentiallyand/or serially. In some embodiments, a first target tissue portionreceives a first thermal dose and a second target portion receives asecond thermal dose.

The method may further comprise the insertion of an ablation device intoa body access device. The body access device may comprise an endoscope.

The method may further comprise positioning the treatment elementproximate the target tissue.

The method may further comprise performing a thermal priming procedure,such as a thermal priming procedure comprising application of negativepressure to at least a portion of the ablation device.

The method may further comprise performing a negative pressure primingprocedure.

The negative pressure priming procedure may remove liquid from theablation device, such as liquid at a non-ablative temperature. Thenegative pressure priming procedure may remove gas bubbles from theablation device.

The thermal dose may further comprise a continuous flow of fluid to andfrom the treatment element. The method may further comprise attaching afluid inflow port of the ablation device to a fluid delivery deviceconfigured to provide this continuous flow of fluid to the treatmentelement. Additionally, the method may further comprise attaching a fluidoutflow port of the ablation device to a negative pressure sourceconfigured to remove a continuous flow of fluid from the treatmentelement. The continuous flow of fluid delivered to the treatment elementmay comprise fluid at a relative constant temperature or fluid whosetemperature changes over time.

The method may further comprise cooling the target tissue, such ascooling performed prior to, during and/or after the application of thethermal dose. The cooling may be performed with one or more coolingmaterials at a temperature less than 37° C. and/or less than 10° C. Thecooling may be performed until at least a portion of the target tissuereaches a steady state temperature. The cooling may be performed for afirst time period and the thermal dose administered for a second timeperiod, wherein the second time period is less than the first timeperiod.

The method may further comprise applying pressure to the target tissueand/or tissue proximate the target tissue, such as to cause a reductionof perfusion in the target tissue and/or tissue proximate the targettissue.

The method may further comprise negative pressure to a body lumen tocause target tissue to contact the treatment element, such as when thetarget tissue comprises tubular target tissue.

The method may further comprise confirming adequate apposition of thetarget tissue with the treatment element. Adequate apposition may beconfirmed prior to and/or during thermal dose delivery. Confirmation maybe performed using a leak test and/or a pressure measurement.

The method may further comprise performing a tissue layer expansionprocedure. The tissue layer expansion procedure may comprise expansionof submucosal tissue, such as by injecting fluid into the submucosaltissue. The tissue layer expansion procedure may be performed withinthirty minutes, such as within fifteen minutes of delivery of thethermal dose to the target tissue.

The method may further comprise radially expanding tubular tissue. Theradial expansion may be performed by a tissue manipulating device and/oran insufflation procedure. The radial expansion may reduce one or moretissue folds.

The method may further comprise stopping delivery of the thermal dose.Stopping delivery of the thermal dose may be accomplished by one or moreof: radially expanding the target tissue; radially compacting thetreatment element; cooling the target tissue; and cooling the treatmentelement.

The method may further comprise monitoring the progress of the thermaldose delivery. The monitoring may comprise an assessment of residualheat. The monitoring may comprise an analysis of one or more signalsreceived from one or more sensors. In some embodiments, the one or moresensors may comprise a temperature sensor. In some embodiments, the oneor more sensors comprise at least one sensor selected from the groupconsisting of: heat sensors such as thermocouples; impedance sensorssuch as tissue impedance sensors; pressure sensors; blood sensors;optical sensors such as light sensors; sound sensors such as ultrasoundsensors; electromagnetic sensors such as electromagnetic field sensors;and combinations of these.

The method may further comprise monitoring the impact of the thermaldose on non-target tissue.

The method may further comprise rotating and/or translating thetreatment element.

The method may further comprise the delivery of a second thermal dose totarget tissue. The second thermal dose may be delivered to the sametarget tissue and/or a second target tissue, such as second targettissue which overlaps the first target tissue. The second thermal dosemay be delivered by the treatment element or a second treatment element.

According to another aspect of the invention, a method for treatingtarget tissue comprises inserting a balloon of a treatment device intothe small intestine; inflating the balloon with a heated fluid;delivering an ablative thermal dose to target tissue; measuring andcontrolling the temperature, pressure and/or flow rate of the deliveredfluid; measuring temperature, flow rate and/or other parameters as afunction of time within or between inflation cycles; applyinginterpretive algorithms to gathered data so as to assess treatmentprogress and make adjustments as needed; and maintaining the inflatedballoon in contact with intestinal mucosa for a period of timesufficient to effect ablation of substantially all of the intestinalmucosa for the desired portion of intestine over the course of one orseveral inflation cycles.

The method may further comprise deflating the balloon to a state inwhich heat transfer to the mucosa has stopped. Alternatively oradditionally, the method may further comprise insufflating the smallintestine to a diametric configuration in which heat transfer to themucosa has stopped.

The method may further comprise removing the balloon from the smallintestine.

The method may further comprise moving the balloon to additionallocations within the intestine and delivering a similar or dissimilarablative thermal dose at each location.

The balloon may comprise a compliant balloon. The balloon may beconstructed and arranged to contact a full circumferential portion ofthe intestinal mucosa.

The method may further comprise controlling the temperature and pressureof heated fluid in the treatment element.

The delivery of the ablative thermal dose may comprise delivering a hotfluid bolus of fixed heat content to the balloon during one or moreinflation cycles.

BRIEF DESCRIPTION OF THE DRAWINGS

The advantages of the technology described above, together with furtheradvantages, may be better understood by referring to the followingdescription taken in conjunction with the accompanying drawings. Thedrawings are not necessarily to scale, emphasis instead generally beingplaced upon illustrating the principles of the technology.

FIG. 1 is a side view of an ablation device positioned in a body lumen,the ablation device comprising an expandable balloon, consistent withthe present inventive concepts.

FIG. 2 is a side view of an ablation device positioned in a body lumen,the ablation device comprising an inner shaft, an outer shaft and anexpandable balloon, consistent with the present inventive concepts.

FIG. 3 is a quasi-steady-state temperature profile generated using theablation device of FIG. 2, consistent with the present inventiveconcepts.

FIGS. 4A and 4B are side views of an ablation device positioned in abody lumen, shown with two directions of hot fluid delivery, consistentwith the present inventive concepts.

FIG. 5 is a transient tissue temperature profile generated using thedevice described in reference to FIGS. 4A and 4B, consistent with thepresent inventive concepts.

FIGS. 6A, 6B and 6C are side views of an ablation device positioned in abody lumen, shown in unexpanded, partially expanded and fully expandedviews, respectively, consistent with the present inventive concepts.

FIG. 6D provides a magnified view of the distal portion of the ablationdevice of FIG. 6C, consistent with the present inventive concepts.

FIG. 7 is a graph of pressure curves for an expandable balloon,consistent with the present inventive concepts.

FIG. 8 is a side view of an ablation device positioned in a body lumen,the ablation device comprising an element to prevent luminal collapse,consistent with the present inventive concepts.

FIG. 8A is an end sectional view of the device of FIG. 8, consistentwith the present inventive concepts.

FIG. 9 is a side view of an ablation device positioned in a body lumen,the ablation device comprising an element to prevent luminal collapse,consistent with the present inventive concepts.

FIG. 9A is an end sectional view of the device of FIG. 9, consistentwith the present inventive concepts.

FIGS. 10A and 10B are side views of an ablation device positioned in abody lumen, the ablation device comprising a translatable shaft, shownin unexpanded and expanded states, respectively, consistent with thepresent inventive concepts.

FIGS. 11A and 11B are side views of an ablation device positioned in abody lumen, the ablation device comprising a fluid delivery tube with avalve, shown in unexpanded and expanded states, respectively, consistentwith the present inventive concepts.

FIGS. 12A, 12B and 12C are side views of an ablation device positionedin a body lumen, the ablation device comprising a dual chamber balloon,shown in fully inflated, partially deflated, and fully deflated states,respectively, consistent with the present inventive concepts.

FIG. 13 is a side view of an ablation device positioned in a body lumen,the ablation device comprising a heater coil, consistent with thepresent inventive concepts.

FIG. 14 is a side view of an ablation device positioned in a body lumen,the ablation device comprising multiple nozzles for directing flow ofheated fluid, consistent with the present inventive concepts.

FIG. 15 is a side view of an ablation device positioned in a body lumen,the ablation device comprising flow directors for directing flow ofheated fluid, consistent with the present inventive concepts.

FIG. 16 is a side view of an ablation device positioned in a body lumen,the ablation device comprising an expandable balloon with one or moresurface modifications, consistent with the present inventive concepts.

FIG. 17 is a side view of an ablation device positioned in a body lumen,the ablation device comprising an expandable balloon with a permeableportion, consistent with the present inventive concepts.

FIG. 18 is a flow chart of a method of ablating tissue, consistent withthe present inventive concepts.

FIG. 19 is a schematic view of a system for treating tissue, consistentwith the present inventive concepts.

DETAILED DESCRIPTION OF THE DRAWINGS

Reference will now be made in detail to the present embodiments of theinventive concepts, examples of which are illustrated in theaccompanying drawings. Wherever practical, the same reference numberswill be used throughout the drawings to refer to the same or like parts.

It is an object of the present inventive concepts to provide systems,methods and device for safely and effectively ablating a volume oftissue (the “target tissue”), such as one or more layers of a portion oftubular or solid tissue, such as tissue of an organ or tissue of thegastrointestinal tract of a patient. The systems and device of thepresent inventive concepts include one or more treatment elements totreat the target tissue, such as expandable treatment elementsconfigured to be expanded to contact the target tissue and/or treatmentelements configured to be positioned at a location to which targettissue is manipulated toward. A treatment element may be configured totreat target tissue in one or more locations of the patient, such as oneor more contiguous or discontiguous locations. The target tissuecomprises a three dimensional volume of tissue, and may include a firstportion, a treatment portion, whose treatment has a therapeutic benefitto a patient; as well as a second portion, a safety margin portion,whose treatment has minimal or no adverse effects to the patient.Non-target tissue may be identified comprising tissue whose treatment bythe treatment element is reduced or avoided.

The target tissue treatment may include one or more effects to thetarget tissue such as an effect selected from the group consisting of:modification of cellular function; cell death; apoptosis; instant celldeath; cell necrosis; denaturing of cells; removal of cells; andcombinations of these. Target tissue may be selected such that aftertreatment the treated target tissue and/or tissue that replaces thetarget tissue functions differently than the pre-treated target tissue.The modified and/or replacement tissue may have different secretions orquantities of secretions than the pre-treated target tissue, such as totreat diabetes or obesity. The modified and/or replacement tissue mayhave different absorptive properties than the target tissue, such as totreat diabetes; obesity and/or hypercholesterolemia. The effect of thetreatment may occur acutely, such as within twenty four hours, or afterlonger periods of time such as greater than twenty four hours or greaterthan one week.

Target tissue to be treated may comprise two or more tissue portions,such as a first tissue portion treated with a first treatment and/or afirst treatment element, and a second tissue portion treated with asecond treatment and/or second treatment element. The first and secondtissue portions may be adjacent and they may contain overlapping volumesof tissue. The first and second treatment and/or treatment elements maybe similar or dissimilar. Dissimilarities may include type and/or amountof energy to be delivered by an energy delivery treatment element. Otherdissimilarities may include but are not limited to: target tissue areatreated; target tissue volume treated; target tissue length treated;target tissue depth treated; target tissue circumferential portiontreated; energy delivery type; energy delivery rate and/or amount; peakenergy delivered; average temperature of target tissue treatment;temperature profile of target tissue treatment; duration of targettissue treatment; and combinations of these.

Target tissue may include tissue of the duodenum, such as tissueincluding all or a portion of the mucosal layer of the duodenum, such asto treat diabetes or obesity while leaving the duodenum anatomicallyconnected after treatment. Replacement tissue may comprise cells thathave migrated from one or more of gastric mucosa; jejunal mucosa; and/oran untreated portion of the duodenum whose mucosal tissue functionsdifferently than the treated mucosal tissue functions prior totreatment. In some embodiments, target tissue includes treatment tissuecomprising the mucosal layer of the duodenum, and safety margin tissuecomprising a full or partial layer of the submucosal layer of theduodenum. In some embodiments, the target tissue comprises the entirelength of the mucosal layer of the duodenum, and may include a portionof the pylorus contiguous with the duodenal mucosa and/or a portion ofthe jejunum contiguous with the duodenal mucosa. Treatment of duodenaltissue may be performed to treat a disease or disorder selected from thegroup consisting of: diabetes; obesity; insulin resistance; a metabolicdisorder and/or disease; and combinations of these. A fullcircumferential portion (e.g. 360°) of the mucosal layer is typicallytreated.

Target tissue may comprise tissue of the terminal ileum, such as totreat hypercholesterolemia or diabetes. In this embodiment, the targettissue may extend into the proximal ileum and/or the colon.

Target tissue may comprise gastric mucosal tissue, such as tissueregions that produce ghrelin and/or other appetite regulating hormones,such as to treat obesity or an appetite disorder.

Target tissue may comprise bladder wall tissue, such as to treat adisease or disorder selected from the group consisting of: interstitialcystitis; bladder cancer; bladder polyps; pre-cancerous lesions of thebladder; and combinations of these.

Target tissue may comprise tissue selected from the group consisting of:large and/or flat colonic polyps; margin tissue remaining after apolypectomy; and combinations of these. These tissue locations may betreated to treat residual cancer cells.

Target tissue may comprise airway lining tissue, such as to treat adisease or disorder selected from the group consisting of:bronchoalveolar carcinoma; other lung cancers; pre-cancerous lunglesions; and combinations of these.

Target tissue may comprise at least a portion of the intestinal tractafflicted with inflammatory bowel disease, such that Crohn's disease orulcerative colitis may be treated.

Target tissue may comprise tissue of the oral cavity, such as to treatone or more of: oral cancers and a pre-cancerous lesion of the oralcavity.

Target tissue may comprise tissue of the nasopharynx, such as to treatnasal polyps.

Target tissue may comprise gastrointestinal tissue selected to treatCeliac disease and/or to improve intestinal barrier function.

The treatment elements, systems, devices and methods of the inventiveconcepts may be constructed and arranged to reduce or avoid treatingcertain tissue, termed “non-target tissue” herein. Depending on thelocation of treatment, different non-target tissue may be applicable. Incertain embodiments, non-target tissue may comprise tissue selected fromthe group consisting of: the tunica serosa, the tunica muscularis and/orthe outermost partial layer of the submucosa such as during mucosaltreatment; Ampulla of Vater such as during mucosal treatment proximatethe Ampulla of Vater; pancreas; bile duct; pylorus; and combinations ofthese.

It is another object of the present inventive concepts to provide adevice for delivering a suitable thermal dose, “thermal dose” definedherein to be the combined effect on the target tissue of thermalapplication time and thermal application temperature. This thermal doseis typically selected to effect ablation of the target tissue bytransferring thermal energy from a heated fluid contained within aballoon. In an alternative embodiment, a chilled fluid may be used tocryoablate the target tissue, similarly with a thermal application timeand a thermal application temperature. The term “fluid” as used hereinshall be understood to refer to any flowable material, includingliquids, gases and gels, such as one or more materials configured to bedelivered to a treatment element such as a balloon, and to deliver athermal dose to target tissue. The thermal dose may be of apre-determined magnitude and/or it may be selected and/or modifiedduring treatment. During the treatment, target tissue ablation may bemonitored and/or adjusted. A dynamic endpoint for treatment may bedetermined through ablation monitoring, such as an endpoint determinedby one or more factors measured during delivery of the thermal dose orduring a non-treatment dose such as a calibrating dose. The device maybe part of a system which includes a controller, such as for providinghot fluid to the balloon and for monitoring and controlling temperatureand/or pressure of the balloon fluid.

The present inventive concepts provide a method for ablating the mucosaof a portion of the small intestine, comprising the steps of: insertinga balloon of a treatment device into the small intestine, such as acompliant balloon; inflating the balloon with a heated fluid so that theballoon is in contact with substantially all of the mucosa for whichnecrosis or other treatment is desired; delivering an ablative thermaldose to the target tissue such as by controlling the temperature andpressure of the fluid during the treatment time or by delivering a hotfluid bolus of fixed heat content to the balloon during one or severalinflation cycles; measuring and controlling the temperature, pressureand/or flow rate of the delivered fluid by associated measuring and/orcontrolling means, including but not limited to, sensors, heaters,pumps, valves, and ballasts where the measuring and/or controlling meansmay be external to the patient's body or may reside in part orcompletely within the treatment device itself; measuring temperature,flow rate and/or other parameters as a function of time within orbetween inflation cycles and applying interpretive algorithms to thegathered data so as to assess treatment progress and make adjustments asneeded; maintaining the inflated balloon in contact with the mucosa fora period of time sufficient to effect ablation of substantially all ofthe mucosa for the desired portion of intestine over the course of oneor several inflation cycles; deflating the balloon to a state in whichheat transfer to the mucosa is stopped; and removing the balloon fromthe small intestine or moving the balloon to additional locations withinthe intestine such that the foregoing treatment cycle may be repeateduntil all of the target tissue has been treated. Treatment of additionallocations may comprise treating contiguous and/or overlapping tissuesegments. Treatment of a second location may be performed after a timeperiod which is initiated after completion of treatment of a firstlocation, such as after a time period configured to allow one or moreportions of tissue to cool, such as to cool to body temperature.

The inventive concepts relate to the conductive transfer of heat from ahot fluid, which is contained within an inflatable balloon, to the innersurface of a body organ. Additionally or alternatively, cryoablation byfluids at low temperatures can be performed. Living tissue may beselectively ablated by the application of heat through a combination oftime and temperature. Elevated temperature ablation of living tissueexhibits a temperature threshold, below which the application of heatover any time duration, short or long, is non-destructive of tissue andabove which the application of heat is increasingly damaging withincreasing time and/or temperature, to the point of necrosis. Thiselevated temperature threshold, as well as the amount of tissue damagethat results over time during application of heat above this threshold,may be different for different cells or organ types and may derive inpart from the natural perfusion of blood through living tissues and theconsequent dissipation of applied heat by the flowing blood. Systems,methods and devices of the present inventive concepts may be configuredto treat a first tissue type and/or a first tissue location with adifferent thermal dose than the thermal dose used to treat a secondtissue type and/or second tissue location, respectively, such as due tothe local perfusion or other local tissue parameter.

In the embodiments described in reference to the figures herebelow,rapid and efficient heat transfer from a balloon to target tissue isachieved via a heat transfer fluid, either delivered as a hot fluidbolus (e.g. the administration of one or more individual, treatmentelement-filling volumes of hot fluid), or continuously delivered asre-circulating hot fluid. Suitable fluids include high heat capacityfluids, such as biocompatible fluids such as water or saline, as well asfluids with high thermal conductivity, such as perfluorinated compounds.

As described herein, room pressure shall mean pressure of theenvironment surrounding the systems and devices of the present inventiveconcepts, sometimes referred to as gauge pressure. Positive pressureincludes pressure above room pressure or a pressure that is greater thananother pressure, such as a positive differential pressure across afluid pathway component such as a valve. Negative pressure includespressure below room pressure or a pressure that is less than anotherpressure, such as a negative differential pressure across a fluidcomponent pathway such as a valve. Negative pressure may include avacuum but does not imply a pressure below a vacuum.

The balloons of the present inventive concepts may be divided into twogeneral categories: those that are composed of a substantially elasticmaterial, such as silicone, latex, low-durometer polyurethane, and thelike; and those that are composed or a substantially inelastic material,such as polyethylene terephthalate (PET), nylon, high-durometerpolyurethane and the like. A third category includes balloons whichinclude both elastic and inelastic portions. Within the category ofelastic balloons, two subcategories exist: a first sub-category whereina combination of material properties and/or wall thickness may becombined to produce a balloon that exhibits a measurablepressure-threshold for inflation, i.e. the balloon becomes inflated onlyafter a minimum fluidic pressure is applied to the interior of theballoon; and a second sub-category, wherein the balloon expandselastically until an elastic limit is reached which effectivelyrestricts the balloon diameter to a maximum value. It will be understoodthat the individual properties of the balloons in each of thesecategories may be applied to one or more advantages in the specificembodiments disclosed herein, these properties integrated singly or incombination. By way of example only, one or more of the followingconfigurations may be employed: a highly elastic balloon may be used toachieve a wide range of operating diameters during treatment, e.g.during operation a desired balloon diameter may be achieved byadjustment of a combination of fluid temperature and pressure; asubstantially inelastic balloon or a balloon that reaches its elasticlimit within a diameter approximating a target tissue diameter (e.g. aduodenal mucosal diameter) may be used to achieve a relatively constantoperating diameter that will be substantially independent of operatingpressure and temperature; a balloon with a pressure-threshold forinflation may be used to maintain an uninflated diameter duringrelatively low pressure conditions of fluid flow and then achieve alarger operating diameter at higher pressure conditions of flow.Pressure-thresholded balloons may be configured in numerous ways. In oneembodiment, a balloon is configured to have a relatively thick wall inits uninflated state, such as to minimize heat transfer out of theballoon and into the surrounding tissue while the balloon is maintainedin this uninflated state. The balloon may be further configured suchthat its wall thickness decreases during radial expansion (e.g. as isdescribed in reference to FIGS. 6A-6D herebelow). In another embodiment,a balloon is configured to have a relatively small diameter in itsuninflated state (e.g. a diameter small relative to the inner diameterof tubular target tissue such as the diameter of the mucosal layer ofduodenal wall tissue), such as to minimize or completely eliminateapposition between the balloon and the surrounding tissue to minimizeheat transfer into the surrounding tissue until the balloon is fullyinflated. In another embodiment, a balloon and device are configured tocirculate a flow of hot fluid through the balloon (e.g. an elasticballoon or an inelastic balloon) at a sufficiently low enough pressureto prevent apposition of the balloon with target tissue, such as topre-heat one or more surfaces of the ablation system and/or ablationdevice that are in fluid communication with the balloon. In thisconfiguration, when the balloon is fully inflated, the temperature ofthe fluid of the balloon will be at a desired level or it will rapidlyand efficiently reach the desired level for treatment (i.e. minimal heatloss to the fluid path components due to the pre-heating). Theseconfigurations provide a method of “thermal priming” prior to targettissue treatment, whereby the balloon and its fluid delivery system areplaced in a state of maximum readiness for the administration of heat tothe target tissue, such as to avoid delays due to undesired cooling fromone or more fluids or device components at a lower temperature than thehot fluid delivered to the balloon for treatment. Alternatively, asimilar procedure may be performed with a chilled fluid, such as whenthe balloon is configured to cryoablate tissue. Each of theseconfigurations is useful singly and in combination for those cases wherethe treatment temperature in the balloon must be established veryrapidly upon inflation. For example, a balloon with a pressure thresholdfor inflation may also, upon inflation, reach its elastic limit within adiametric range applicable to the target tissue being treated. In someembodiments, priming such as thermal priming may include a purge with agas (e.g. air) prior to the delivery of the priming fluid. In someembodiments, priming such as thermal priming may include an evacuationprocedure prior to the delivery of the priming fluid. Presence of gasbubbles may lead to undesired non-uniform or otherwise inaccuratetransfer of heat energy to the target tissue. A fluid evacuation stepmay comprise application of a vacuum or other negative pressure sourceto one or more fluid pathways to subsequently be primed or otherwisefilled, such as to eliminate or otherwise reduce gas bubbles. Theadvantages of these embodiments as they relate to various treatmentconditions and modalities are described immediately herebelow inreference to a first treatment modality and a second treatment modality,and will be further elaborated in reference to the figures describedherein.

Treatment Modality 1: APPOSITION BETWEEN THE BALLOON AND THE TARGETTISSUE IS ESTABLISHED BY ADJUSTING THE BALLOON DIAMETER. At those timesduring treatment when it is desirable to increase or otherwise modifyheat transfer between the balloon and the target tissue, the balloondiameter may be increased in situ so as to conform to the nativediameter of the target tissue, such as to the native diameter of tubulartissue such as duodenal wall tissue. At those times during treatmentwhen it is desirable to decrease heat transfer between the balloon andthe target tissue, the balloon diameter may be reduced in situ, such asto prevent or reduce contact of the balloon with the target tissue. Forthose cases where the native diameter of the tissue varies substantiallywithin the treatment zone, then a highly elastic or compliant balloonmay be employed, such as a balloon which may be adjusted to achieve awide range of operating diameters. For those cases, where ashort-duration thermal treatment is desired, as for example, a thermaldose application of less than 30 second duration, then apressure-threshold balloon may be used, such as when thermal priming isemployed prior to inflation.

Treatment Modality 2: APPOSITION BETWEEN THE BALLOON AND THE TARGETTISSUE IS ESTABLISHED BY CONTROLLING THE DIAMETER OF THE TARGET TISSUE.To initiate and/or increase heat transfer between a treatment element,such as a balloon, and the target tissue, the diameter of the targettissue may be decreased in situ so as to approximate and/or conform tothe diameter of the balloon. To decrease heat transfer between thetreatment element, such as a balloon, and the target tissue, thediameter of the target tissue may be increased in situ, so as to preventor reduce contact of tissue (e.g. target tissue or non-target tissue)with a treatment element. The diameter of the tissue proximate atreatment element may be increased or decreased, independently of thetreatment element diameter, by means of a variety of fluids that may beadministered within and/or withdrawn from the target-tissue lumen, suchas using insufflation techniques knows to those of skill in the art.Typical insufflation fluids include but are not limited to: gases suchas CO₂ or air; liquids such as saline solution; and combinations ofthese. The insufflation fluids may be introduced through the ablationdevice, through an endoscope such as an endoscope through which theablation device is inserted, or via another device placed proximate thetarget tissue. Delivery of insufflation fluids may be performed tomanipulate tissue such as to distend tissue. Alternatively oradditionally, delivery of insufflation fluids may be performed to movetarget tissue away from a treatment element, such as to stop transfer ofenergy to target tissue at the end of a thermal dose period. Removal ofthese insufflation fluids and/or the application of a vacuum or othernegative pressure by one or more of the devices described immediatelyhereabove, can be used to decrease the diameter of the target tissue,such as to bring the target tissue in contact with a treatment element.In this tissue diameter controlled approach, a balloon that may bemaintained at a substantially constant diameter may be desirable, suchas a substantially inelastic balloon such a balloon with anelastic-limit. When a short-duration thermal treatment is desired, asfor example, a thermal application of less than 30 second duration, thena pressure-thresholded balloon may also be desirable.

Referring now to FIG. 1, a tissue treatment device with its treatmentelement positioned in a body lumen is illustrated, in accordance withthe present inventive concepts. Device 100 includes shaft 110 havingproximal end 111 and distal end 112. Device 100 also includes balloon120, positioned on a distal portion of shaft 110 and configured to beinflated by introducing fluid into a lumen 113 which exits shaft 110through opening 114, such that balloon 120 expands to contact targettissue, such as the luminal wall tissue shown in contact with balloon120. Opening 114 may comprise multiple openings, not shown. Opening 114may be positioned in one or more locations, such as to adjust the flowdynamics of fluid delivered into and/or removed from balloon 120.Inflation of balloon 120 with hot fluid delivers thermal energy to thetarget tissue through the wall of balloon 120. Balloon 120, and theother balloons of the inventive concepts provided herein, may comprise acompliant balloon; a non-compliant balloon; a balloon with a pressurethreshold; a balloon with compliant and non-compliant portions; andcombinations of these. In the illustrated embodiment, the thermal doserequired to limit ablation to a thin inner layer of a target tissue isachieved by means of a heated fluid “bolus” (i.e. a fixed mass of hotfluid) that is injected into an empty or deflated balloon, for example,balloon 120 (shown in an inflated state in FIG. 1). As shown, theprecise mass of fluid that is injected into balloon 120 may becontrolled by controlling the volume delivered (as by a syringe 150positioned at proximal end 111 and in fluid communication with lumen113). In an alternative embodiment, the precise mass of fluid that isinjected into balloon 120 can be controlled through pressure control ormeasurement, such as by pressure regulation during balloon inflation. Insome embodiments, balloon 120 is an inelastic balloon or otherwisereaches an elastic limit, and the mass of fluid is achieved (i.e.controlled) when balloon 120 is completely filled, for example when acomplete fill is confirmed when a rapid rise in balloon pressure occurs(e.g. as detected by one or more pressure sensors, not shown but influid communication with balloon 120 and/or in contact with balloon120). In some embodiments, balloon 120 is an elastic balloon and themass of fluid is achieved based on a predetermined delivery volumeand/or when the pressure in balloon 120 reaches a pre-determinedpressure or balloon 120 reaches a pre-determined amount of stretch (e.g.as measured by a strain gauge mounted in or on balloon 120). As anelastic balloon 120 is filled with fluid, pressure will increasecontinuously, typically at an expected rate, until apposition withtissue is initiated. Additional fluid delivered causes the pressure tochange at an increased rate (i.e. higher change of pressure per unitvolume of fluid delivered after initial apposition). Pressure measuredat the inflexion point (i.e. at the change in rate of pressureincrease), hereinafter “apposition pressure”, represents the pressurenecessary to achieve initial apposition of balloon 120 with tissue atthat particular target tissue location. In some embodiments, amount offluid delivered to balloon 120 comprises a volume of fluid whosedelivery causes balloon 120 to be pressurized at the appositionpressure. In other embodiments, additional fluid is delivered to causeballoon 120 to be pressurized to a level above apposition pressure, suchas a predetermined amount of additional fluid or an amount of additionalfluid delivered to achieve a predetermined increase in pressure aboveapposition pressure. Device 100 may be configured to regulate pressurewithin balloon 120 to provide a function selected from the groupconsisting of: maintaining a thermal profile; expanding balloon 120 to adesired diameter; expanding the target tissue to a desired diameter;distending the target tissue; compressing a layer of the target tissuesuch as a mucosal layer; and combinations of these. When the mass of thethermal dose bolus is fixed, the values of temperature and heat capacityof the fluid determine the total heat content of the injected bolus andthereby determine the maximum deliverable thermal dose for a giveninflation cycle of balloon 120.

For a given starting temperature of the bolus, the time duration of theheat application may be less critical or less specifically controlledsince the total treatment energy delivered is based primarily on thisstarting bolus temperature. A complete cycle of this particularembodiment is understood to comprise the rapid inflation of the balloonwith a heated bolus of fluid, the temperature decay of the bolus toeither a sub-threshold level or to any pre-determined temperature levelas it transfers heat to the target tissue, and the subsequent emptyingof balloon 120 (e.g., by an applied vacuum or other negative pressureapplied to lumen 113). In some embodiments, one or several repeat hotfluid fill and emptying cycles may be applied to the target tissue toeffect complete treatment at any given location. Each cycle may comprisea similar or dissimilar starting bolus temperature.

By consideration of the heat transfer properties of the hot fluid in theballoon and the balloon material, as well as the heat transferproperties of the target tissue (including the composition of the tissueand the rate of blood perfusion within the tissue), along with the heattransfer properties at the interface between balloon 120 and the targettissue, the correct temperature of the bolus may be selected toeffectively ablate the target tissue. Collectively, these various heattransfer properties are manifested in a single measurable variable: thetemperature decay rate of the bolus, which may be monitored by one ormore temperature sensors 130 that are positioned on, within the wall of,and/or within the cavity of balloon 120. Signals received from the oneor more temperature sensors 130 are interpreted through one or moretreatment algorithms, as are described herebelow. Temperature sensors130 may be positioned to measure the temperature of target tissue,tissue proximate target tissue, and/or non-target tissue. One or morealgorithms of device 100 may use the signals provided by the one or moresensors 130 to adjust the thermal dose, such as to adjust thetemperature of one or more fluids delivered to and/or circulating withinballoon 120, and/or to cause balloon 120 to rapidly deflate, ceasingdelivery of thermal energy from balloon 120 to the target tissue.Ceasing of energy delivery may also be caused by radial expansion oftubular target tissue, such as via an insufflation of gastrointestinalor other luminal wall tissue as is described hereabove. Device 100 mayinclude control means, such as those described in reference to FIG. 19herebelow, such that one or more algorithms can control fluid deliverybased on signals from the one or more sensors 130. An algorithm mayaccount for the distance between the sensor and the treatment elementand/or the distance between the sensor and the target tissue.

The state of necrosis of the target tissue and the health of anyunderlying, non-target tissue may be monitored by monitoring the rate oftemperature decay of the applied bolus. The rate of temperature decay isrelated to the perfusion rate of blood through the target tissue andthrough the underlying tissue. Therefore, the necrosis of the targettissue and the associated shut-down of perfusion within that tissue isexpected to be accompanied by a reduction in the rate of heat transfer.Simultaneously, the continuing perfusion and therefore the continuingviability of the non-targeted underlying tissue will be indicated by aminimum rate of temperature decay. The rate and shape of the temperaturedecay curve of the bolus carries useful information, such as informationused to monitor the progress of the ablation and/or to optimize thetarget tissue treatment. The temperature decay curve may be monitoredprecisely by means of one or more temperature sensors 130. Such sensors130 typically include one or more sensors selected from the groupconsisting of: thermocouple; thermistor; resistance temperature detector(RTD); optical pyrometer; fluorometer; and combinations of these.Additionally or alternatively, device 100 may include one or more othersensors 131, such as one or more other sensors constructed and arrangedto measure: pressure such as fluid pressure; flow rate; temperaturesensor such as a fluid temperature sensor; viscosity; density; opticalclarity; and combinations thereof. Alternatively or additionally,sensors 131 may comprise one or more sensors constructed and arranged tomeasure a parameter selected from the group consisting of: tissueimpedance such as electrical impedance and thermal impedance; tissuecolor; tissue clarity; tissue compliance; tissue fluorescence; andcombinations thereof. In one embodiment, sensor 131 comprises a forcesensor constructed and arranged to measure the physical contact betweenthe expandable treatment element and the target tissue. In anotherembodiment, sensor 131 comprises a strain gauge positioned on theexpandable treatment element. In another embodiment, sensor 131 ispositioned on device 100, such as a sensor selected from the groupconsisting of: a sensor positioned to contact target tissue or othertissue; a pressure sensor; a temperature sensor; a sensor attached to anexternal portion of balloon 120; a sensor positioned within a wall ofballoon 120; and combinations of these.

In one embodiment, optimization of a treatment cycle may be achieved byadjusting temperature and duration in one or more cycles and/or byterminating one or more cycles, such as an adjustment or terminationbased upon observed changes in the shape of the temperature decay curve.In some embodiments, ablation may be approached in incremental steps,such as by applying a first “calibration bolus” to the target tissue,for example, a calibration cycle including the application of asub-threshold temperature bolus (e.g. via fluid delivered to balloon 120at 41° C.) for which the natural decay rate of target tissue would berecorded. A subsequent treatment cycle or cycles would then beincrementally increased in temperature such that the evolving shape ofthe decay curve could be quantitatively monitored based on informationrecorded during the calibration cycle, such as to determine the onsetand progress of ablation. An algorithm may include a mathematical modelof the heat transfer into the target tissue based on informationcollected in the calibration cycle. The algorithm may be defined orrefined by empirical correlation, such as via information collected in asecond calibration cycle and/or information collected during one or moretreatment steps.

In some embodiments, the effect of increased blood perfusion due to theapplication of heat to soft tissue can be included in the analysis ofthe temperature decay curve, such as when this effect is found to be asignificant factor when delivering heat energy to the target tissue. Themagnitude of this effect may be determined in a calibration cycle, suchas the calibration cycle described hereabove. Alternatively, the targettissue may be characterized using data from a general patientpopulation, such as data collected prior to the initiation of atreatment cycle. Additionally or alternatively, data from the specificpatient may be used to characterize the target tissue, such as datacollected in a calibration cycle, data collected in a treatment cycle,and/or other data.

Device 100 may be part of an ablation system, such as an ablation systemincluding a temperature controlled fluid delivery device as is describedin reference to FIG. 19 herebelow. Balloon 120, and the other treatmentelements of the present inventive concepts, may be configured to berotated, translated, moved in a helical spiral, or otherwiserepositioned prior to a tissue treatment, during a tissue treatment,after a tissue treatment and/or between treatment of a first portion oftissue and a second portion of tissue. Movement of balloon 120 may bemanual and/or automated, such as via automation provided by one or moremotion transfer mechanisms described in reference to ablation system 300of FIG. 19 herebelow.

FIG. 2 illustrates a device for treating tissue, positioned in a bodylumen and including an inner shaft, an outer shaft, and an expandableballoon, in accordance with the present inventive concepts. Device 100includes a proximal end 111, a distal tip 112 and a shaft 110. Shaft 110includes a lumen 113 therethrough. Lumen 113 is in fluid communicationwith port 163. Positioned within shaft 110 is shaft 164, which surroundslumen 160. Shaft 164 includes port 161 and port 162, each in fluidcommunication with lumen 160. In one embodiment, hot fluid is deliveredto port 161 and fluid having a lower temperature than the hot fluidenters port 162. Fluid delivered through port 162 can be used toincrease or decrease the temperature of the fluid in balloon 120. Fluiddelivered through port 162 can be used to modulate the temperature ofthe fluid in balloon 120. Port 163 is configured to be attached to apumping or negative pressure source configured to create an outflow offluid from lumen 113. Device 100 also includes balloon 120 configured tobe inflated such that balloon 120 contacts target tissue and enablestreatment of the target tissue through the wall of balloon 120. In theillustrated embodiment, the control of the surface temperature ofballoon 120 may be achieved by continuous circulation of hot fluid intoand out of balloon 120 via lumen 160 of shaft 164, which iscircumferentially surrounded by lumen 113. Fluid flowing through lumen113 may be configured as an insulator, reducing undesired cooling offluid flowing through lumen 160 by the cooler environment surroundingshaft 110.

The distal end of lumen 160 is typically positioned in a distal portionof balloon 120, as shown in FIG. 2. The distal end of lumen 113 istypically positioned in a proximal portion of balloon 120, also asshown. Staggered positioning of the exit ports of lumens 160 and 113causes mixing of fluid introduced into balloon 120. While the distal endof lumen 113 is shown positioned at the proximal end of balloon 120,shaft 110 may extend to a more distal portion of the internal volume ofballoon 120, such as to change the flow dynamics within balloon 120.Similarly, the distal end of lumen 160 may be positioned in numerouslocations within balloon 120, such as to modify the flow dynamics withinballoon 120. One or more flow directors may also be included to causefluid mixing, such as those described in reference to FIG. 15 herebelow.In some embodiments shaft 164 is slidingly received by shaft 110, suchthat the distal end of shaft 164 and lumen 160 can be advanced andretracted, such as to modify the flow dynamics within balloon 120.Alternatively or additionally, shaft 110 may be configured to beadvanced and/or retracted, such as to reposition the distal end of lumen160. While lumens 113 and 160 are shown in a concentric geometry, theseand other lumens of the present inventive concepts may be positioned innumerous configurations including but not limited to: concentric;side-by-side; eccentric (e.g. off-center); helical; and combinations ofthese. Device 100 may include a heating element, such as heating element135 positioned within balloon 120. Alternatively or additionally, one ormore heating elements can be positioned in or proximate to a fluidpathway, such as one or more fluid pathways present in lumens 113 and/or160, or one or more fluid pathways in fluid communication with lumens113 and/or 160. A control loop may be established wherein balloon 120surface temperature, as measured with one or more temperature sensors130, serves as a feedback parameter, and the time rate of energytransfer into balloon 120 serves as the control variable. The time rateof energy transfer into balloon 120 can be measured, such as bymeasuring the temperature and/or flow rate of the fluid, the powertransfer into heating element 135, and/or by another measurement, suchas to monitor the progress of the ablation. As discussed in reference toFIG. 1, indications of the onset and progress of ablation are expectedto be manifested by changes in the rate of energy transfer that arerequired to maintain a constant or pre-determined temperature at thesurface of balloon 120. The onset of ablation may be graduallyapproached from treatment cycle to treatment cycle by incrementallyincreasing the temperature level of the treatment element. Theintegrated time rate of energy transfer may provide a means ofmonitoring the total accumulated thermal dose.

In one embodiment, the thermal dose required to limit ablation to arelatively thin, inner layer of target tissue is achieved by means of acontinuously time-varying application of heat. The desired timevariation may be accomplished, for example, by means of a re-circulatinghot-fluid that passes over a modulated heater, such as heater 135,typically a resistive or other heater connected to one or more wires,not shown but traveling proximally and electrically attached to a supplyof power. Alternatively, the desired time variation may be accomplishedby a process of periodic thermal dilution of a re-circulating hot fluid.Thermal dilution is herein defined as the rapid lowering of thetemperature of a circulating heat transfer fluid by means of theintroduction of a second fluid of lower temperature. For example, a hotfluid can be delivered and/or recirculated via port 161, and thermaldilution can be achieved by introducing a fluid of lower temperature viaport 162. In one embodiment, a first fluid at a temperature at or above65° C., such as a temperature between 65° C. and 99° C., will bedelivered to balloon 120 for at least 3-5 seconds, followed by theintroduction of a second fluid at a temperature below 43° C. for atleast 3-5 seconds. In typical embodiments, the first fluid may bedelivered at a temperature of 65° C. for approximately 30-60 seconds, at70° C. for approximately 5-45 seconds, at 75° C. for approximately 3-40seconds, at 80° C. for approximately 3-30 seconds, or at 90° C. forapproximately 3-20 seconds. The second fluid is typically delivered at atemperature at or below 37° C. for at least 15 seconds.

A time-varying application of heat is expected to have severaladvantages including but not limited to: differences between thefrequency, phase and amplitude of the temperature waveforms measured attwo or more locations (e.g. at the balloon's surface and at a locationupstream of the balloon) may be indicative of the progress of thermalablation and therefore offer a means of monitoring ablation inreal-time; continuous modulation of the peak temperature offers a meansof incrementally approaching thermal ablation without the need toinflate and deflate the balloon repetitively, thereby enhancing theprecision of the treatment without prolonging the treatment time;continuous modulation of the peak temperature permits the application ofelevated temperatures during well-controlled periods of short duration,which may help to ensure that the inner-most tissue layer is effectivelyablated by the temperature peaks while simultaneously ensuring that thetissue sub-strata can dissipate heat in the time between peaks; the peaksurface temperature may be ramped up or down in the course ofmodulation, so that a peak ablation temperature may be approachedincrementally; and combinations of these.

In this embodiment, the temperature of balloon 120 surface may be heldsubstantially constant for the duration of the application time at aselected value, and the resulting quasi-steady-state heat transferprofile into and through the target tissue is such as to locate thedamage threshold of the target tissue at or near the intended boundaryfor treatment. The surface temperature is preferably of a value that isslightly higher than the threshold for damage, e.g. at or above 43° C.,typically between 45° C. and 50° C., so that ablation is limited to theinner-most layer of the tissue while the deeper layers are undamaged,such as by maintaining the non-target tissue at a temperature below anecrotic threshold, such as by using the perfusion of blood as a heatsink.

A complete target tissue treatment cycle may comprise the rapidinflation of an empty or deflated balloon with hot fluid so as toestablish uniform and positive contact between the balloon and thetarget tissue; the maintenance of constant and uniform temperature atthe surface of the balloon by means of continuous mixing of the contentsof the balloon in conjunction with the continuous adjustment of the heatflow into and out of the balloon, applied over a time sufficient toestablish quasi-steady-state heat transfer; followed by rapid deflationof the balloon so as to disengage the balloon from contact with thetarget tissue and/or rapid insufflation to radially expand the targettissue (e.g. to stop energy transfer). In some embodiments, one orseveral repeat cycles may be applied to one or more discrete portions ofthe target tissue to effect complete treatment of all target tissueintended to be treated. In one embodiment, inflation of a treatmentelement is accomplished in less than 10 seconds from initiation ofexpansion, typically less than 5 seconds. In another embodiment,deflation of the treatment element and/or radial expansion of the targettissue using insufflation (as described hereabove), such as to removecontact between the target tissue and the treatment element sufficientto eliminate heat transfer, is accomplished in less than 10 seconds,typically less than 5 seconds.

Ports 161, 162 and 163, and each of the other inflow and outflow portsof the present inventive concepts, may each be configured to deliverfluid to balloon 120 and/or to extract fluid from balloon 120. In someembodiments, during single or multiple tissue treatments, ports 161, 162and/or 163 are configured to deliver fluid for a first time period, andextract fluid for a second time period. In one embodiment, a pump ornegative pressure source is provided to perform a negative pressurepriming procedure, defined herein as a procedure to remove a majority offluid from lumen 160, lumen 113 and/or balloon 120, such as to removenon-ablative temperature fluid and/or gas bubbles. A negative pressurepriming procedure may be performed prior to delivering a thermal dosecomprising fluid at an elevated temperature such as a temperature above65° C.

Device 100 typically includes at least one temperature sensor 130constructed and arranged to measure hot fluid and/or balloon 120temperature at any time before, during, or after the target tissuetreatment. Device 100 may include numerous other types of sensors, asare described in reference to FIG. 1 hereabove. Device 100 may be partof an ablation system, such as an ablation system including atemperature controlled fluid delivery device as is described inreference to FIG. 19 herebelow.

FIG. 3 illustrates a quasi-steady-state temperature profile generatedusing the ablation device described in reference to FIG. 2, inaccordance with the present inventive concepts. The illustratedtemperature profile is established within a cross-section of the targettissue, such as the wall of a hollow organ such as the duodenum, whenthe target tissue is assumed to be in efficient thermal contact with aballoon or other treatment element that is filled with a hot-fluid. Thegeneral form of the temperature profile is illustrative for a hot-fluidballoon that is configured to have a time-invariant surface temperature.The temperature profile is herein described as quasi-steady-state,rather than strictly steady-state, because it is to be understood thatthe temperature profile is expected to be slowly and systematicallyvarying, and that the variation is substantially due to the progress ofablation and the associated changes in local perfusion and heat transferthat accompany ablation.

FIGS. 4A and 4B illustrate a device for treating tissue, positioned in abody lumen and including an inner lumen and an outer lumen fordelivering or removing hot fluid from a balloon, in accordance with thepresent inventive concepts. Device 100 includes a proximal end 111, adistal tip 112 and a shaft 110. Shaft 110 includes a lumen 113therethrough. Lumen 113 is in fluid communication with port 163. Port163 is attached to a fluid transfer device, such as a fluid deliverydevice configured to deliver temperature controlled fluid to lumen 113or a fluid extraction device configured to remove fluid from lumen 113.Residing within lumen 113 is shaft 164 which comprises lumen 160therethrough. Lumen 160 is fluidly attached to port 161. Port 161 issimilarly configured to be attached to a fluid transfer device, such asa fluid delivery device configured to deliver temperature controlledfluid to lumen 160 or a fluid extraction device configured to removefluid from lumen 160. Typical fluid delivery and extraction devices aredescribed in reference to FIG. 19 herebelow and are configured toindependently deliver and remove fluid from lumens 113 and 160. Device100 also includes balloon 120 which is configured to be inflated byfluids delivered through lumens 113 and 160 such that balloon 120contacts target tissue and enables treatment of the target tissue viathese fluids. In the embodiment of FIG. 4A, port 161 is attached tofluid delivery device 600, typically a pump or pressurized reservoirconfigured such that fluid flows from lumen 160 into balloon 120. Port163 is attached to fluid extraction device 700, such as a pump orreservoir maintained at a vacuum or other negative pressure sufficientto cause fluid to flow from balloon 120 into lumen 113 and out port 163.Negative pressures can be applied to port 163 by fluid extraction device700 such that the flow from balloon 120 into lumen 113 and out port 163is at a higher level than would otherwise have been achieved if port 163was simply open to or otherwise maintained at room pressure. In analternative embodiment, fluid extraction device 700 creates a pressureabove room pressure but at a level low enough to cause fluid to flowfrom balloon 120 into lumen 113 and out port 163 (e.g. at a pressurelevel below the level of fluid introduced by fluid delivery device 600).In the embodiment of FIG. 4B, the connections are reversed, and port 163is attached to fluid delivery device 600 and port 161 is attached tofluid extraction device 700. Fluid flows from port 163 through lumen 113and into balloon 120. Fluid flows from balloon 120, into lumen 160 andout port 161, as is described in the reverse direction in reference toFIG. 4A hereabove. In an alternative embodiment, a fluid extractiondevice 700 is not included, such that port 163 of FIG. 4A or port 161 ofFIG. 4B is simply unattached to any device or otherwise connected to areservoir at a pressure approximating room pressure, such that rate offluid transferred through balloon 120 is controlled by the fluiddelivery device. Inclusion of fluid extraction device 700 allowsincreased flow of fluid through balloon 120 (e.g. when fluid extractiondevice 700 is operated at a negative pressure), as well as increasedprecision of control of fluid flow (e.g. by controlling the pressuredifferential applied between lumen 113 and lumen 160. It will beunderstood that the arrangement of lumens 113 and 160 may be concentric,as shown in FIGS. 4A and 4B, may be side-by-side, or may be any otherarrangement that provides for the fluid communication to and/or fromballoon 120. One or more of lumens 113 and/or 160 may be reinforced,such as when shaft 110 and/or shaft 164, respectively, comprise areinforced shaft such as a braided or spiral-wire reinforced tubeconfigured to prevent collapse during vacuum or other negative pressurelevel states. Referring to the embodiment of FIG. 4A, both fast thermalrise-time and fast thermal response-time may be achieved for the hotfluid in balloon 120 by delivering fluid at a positive pressure vialumen 160 (e.g. delivering hot fluid through lumen 160) while extractingfluid by applying a negative pressure via lumen 113 (e.g. applying anegative pressure or otherwise withdrawing fluid through lumen 113). Thesimultaneous delivery and withdrawal of fluid maximizes the differentialpressure across balloon 120 and enables high flow rate of fluids throughballoon 120. Referring to the embodiment of FIG. 4B, both fast thermalrise-time and fast thermal response-time are achieved for the hot fluidin balloon 120 by applying a positive pressure via lumen 113 (e.g.delivering hot fluid through lumen 113) while applying a negativepressure via lumen 160 (e.g. applying a negative pressure or otherwisewithdrawing fluid through lumen 160). In some embodiments, a purgingprocedure may be performed prior to the introduction of a hot fluidthermal dose into balloon 120, such as a purging with a fluid such asair. Alternatively or additionally, a negative pressure primingprocedure, as has been described hereabove, may be performed, such as toreduce or eliminate gas bubbles or to remove a fluid at an undesiredtemperature. Purging and/or negative pressure priming procedures may beapplied to one or more fluid pathways of device 100 including but notlimited to: lumen 160, lumen 113 and/or balloon 120. In someembodiments, balloon 120 may be configured to cool tissue, such as acooling procedure performed prior to and/or after the application of athermal dose, as is described in reference to FIG. 18 herebelow.

Thermal rise-time is defined herein as the time duration to reach targettemperature within and/or on the surface of balloon 120 from the startof the inflation period. In a typical embodiment, thermal rise-time israpid, such as a thermal rise time in which fluid temperature reaches90% of a target temperature within 5 seconds of initiating theinflation. Thermal response-time is defined herein as the time durationto reach and maintain an adjusted target temperature within and/or onthe surface of balloon 120. In a typical embodiment, thermal responsetime is rapid, such as a thermal response time in which fluidtemperature reaches 90% of a modified target temperature within 15seconds of initiating the change to the new target temperature. In someembodiments, thermal fall-time is also rapid, such as a thermal falltime in which fluid temperature reaches 110% of body temperature with 15seconds, typically less than 5 seconds.

Thermal rise-time may be affected by whether balloon 120 is in contactwith tissue, the amount of contact, and the temperature of the tissuebeing contacted. Filling of balloon 120 that causes or changes contactwith tissue will impact thermal rise-time, such as to slow down thermalrise time as contact initiates and/or increases. Thermal rise times maybe improved by purging one or more fluid pathways of device 100 with airprior to delivery of hot fluid. Thermal rise times may be improved byapplying a vacuum or other negative pressure to port 163 during deliveryof hot fluid via port 161.

Thermal fall-time may be configured to correlate to the time it takesballoon 120 to reach a temperature that no longer delivers significantenergy to the target tissue. A balloon 120 whose temperature falls belowtarget temperature, for example 5° C., 10° C. and/or 20° C. less than atarget temperature, may be considered to have stopped ablating tissue.Thermal fall times may be improved by purging with air and/or cold fluidafter cessation of the target tissue treatment, such as by applying avacuum or other negative pressure to port 163 and/or delivering coldfluid via port 161, respectively.

In one embodiment, the adjustment of temperature is maintained by one ormore temperature controlling elements that may be used to alter the heatflux passing into and out of balloon 120, including external andinternal heat sources such as resistance heaters, as well as variouselements for controlling fluid flow rate such as pumps, positivepressure sources and negative pressure sources. Heaters of various sortsrely on convective heat transfer; therefore their performance isenhanced by high fluid flow rates. A fast thermal rise-time isadvantageous for several reasons including but not limited to: the totaltreatment time may be reduced, thus minimizing risk and discomfort andcost to the patient; a shorter rise-time reduces variability in thetreatment time and so permits more precise control of the overallthermal dose; and combinations of these. Fast thermal response-time isadvantageous because it enables rapid and precise adjustments in balloontemperature in response to fluctuations measured by temperature sensor130 within balloon 120, which also improves precision in the control ofthe overall thermal dose. Fast thermal fall-times provide advantages aswell, such as to achieve a precise depth of ablation. The ability tostop transfer of heat to tissue can be achieved by a fast thermalfall-time. Alternatively or additionally, a device including a treatmentelement which can be rapidly moved away from tissue (e.g. via balloon120 radial compression and/or target tissue radial expansion) can beused to quickly stop treatment of the target tissue. While heat istransferred from balloon 120 to target tissue, heat is also beingconducted from target tissue to non-target tissue structures. Rapidthermal rise and fall times can be used to minimize amount of undesiredheat transferred to non-target tissue, such as to achieve a shallowthermal gradient during treatment.

In the embodiments shown in FIGS. 4A and 4B, differential pressure ismaximized by simultaneously applying a positive fluid pressure to port163 and a negative pressure (e.g. suction) to port 161, or vice versa,each of which is in fluid communication with balloon 120. While thedifferential pressure across balloon 120 is maintained at a high level,and while the resulting fluid flow rate is also maintained at a highlevel, the pressure within balloon 120 may be maintained at a much lowerlevel than would be achieved with a single positive or negative pressuresource (e.g. fluid delivery device 600 alone). Precise and dual sourceadjustment of balloon 120 pressure is advantageous for several reasons,including but not limited to: the minimum pressure required to establishuniform and positive contact between the balloon and the target tissuemay vary from location to location within an organ and therefore ispreferably an independent control variable which can be adjusted asrequired to optimize the ablation process during the treatment; thesafety of the overall treatment may be improved by minimizing theballoon pressure; and combinations of these.

Device 100 typically includes at least one temperature sensor 130constructed and arranged to measure hot fluid and/or balloon 120temperature at any time before, during, or after the target tissuetreatment. Device 100 may include numerous other types of sensors, asare described in reference to FIG. 1 hereabove. Device 100 may be partof an ablation system, such as an ablation system including atemperature controlled fluid delivery device as is described inreference to FIG. 19 herebelow.

FIG. 5 illustrates a transient tissue temperature profile generatedusing an ablation device as is described in reference to FIGS. 4A and 4Bhereabove, in accordance with the present inventive concepts. In oneembodiment, the thermal dose required to limit ablation to a thin innerlayer of target tissue (e.g. a layer comprising at least the fullmucosal thickness of the duodenum) is achieved by means of a preciselycontrolled application of a hot fluid balloon operating at atime-average temperature over a well-controlled time interval. In thisembodiment, the time interval during which heat is applied to the targettissue is understood to be shorter than would be required to achieve aquasi-steady-state temperature profile, as described and shown in FIG. 3hereabove, within and across the target tissue cross-section. Therefore,the temperature profile is transient and the location of the boundaryfor necrosis within the tissue cross-section is a strong function oftime and temperature such that both parameters must be controlled withprecision in order to limit necrosis to a thin inner layer of the targetorgan.

FIGS. 6A-6C, illustrate a device for treating tissue, positioned in abody lumen and including an expandable element, shown in unexpanded,partially expanded, and fully expanded states, respectively, inaccordance with the present inventive concepts. FIG. 6D illustrates amagnified view of the distal portion of the device of FIG. 6C. Device100 is of similar construction, and includes components similar todevice 100 of FIGS. 4A and 4B. Device 100 further includes a positioningassembly 115 configured to position the treatment element, balloon 120,relative to tissue, such as target tissue and/or non-target tissue. Thepositioning assembly comprises an expandable cage 118 which is attachedto deployment shaft 116 and a floating tube 117. The proximal end ofshaft 116 includes grip 119, configured as a grip point for an operatorto advance and/or retract shaft 116. Floating tube 117 is slidinglyreceived by device 100 distal portion 112. Advancement of shaft 116causes floating tube 117 to move distally and expandable cage 118 toelongate and radially compress, as shown in FIG. 6A. Retraction of shaft116 causes floating tube 117 to move proximally and expandable cage 118to shorten and radially expand, as shown in FIGS. 6B, 6C and 6D.Positioning assembly 115 may be configured to position an expandabletreatment element, such as balloon 120, in its expanded and/orunexpanded states, in the center of a body lumen (as shown) or at anoff-center location. Positioning assembly 115 may be configured to movea treatment element, such as balloon 120, in a partially expanded orunexpanded state, away from tissue, such as a rapid movement occurringin less than 5 seconds, typically less than 1 second, such as to preventcontinued transfer of energy from balloon 120 to tissue. Whilepositioning assembly 115 of FIGS. 6A-6C comprises an expandable cage,numerous radially deployable mechanisms could be employed to position atreatment element relative to tissue, such as expandable balloons,radially deployable arms, and the like. Expandable cage 118 and/or otherpositioning elements of positioning assembly 115 may be placed at thesame longitudinal location as balloon 120 (as shown, in FIGS. 6A-C), orat a location proximal and/or distal to balloon 120. In someembodiments, expandable cage 118 is configured to move tissue away fromballoon 120 (e.g. to further expand from the configuration shown in FIG.6D), such as to stop delivery of energy to tissue. Positioning assembly115 may be integral to device 100 (as shown in FIGS. 6A-6D), or it maybe a separate device configured to position a treatment element, such asballoon 120, relative to tissue, such as target or non-target tissue.

Device 100 may be configured to allow thermal priming to be performed onballoon 120, where thermal priming is defined as the process ofpre-heating at least a portion of balloon 120 material and/or theconduits leading to balloon 120, as has been described in detailhereabove. The pre-heating is typically performed prior to balloon 120inflation, such as to heat fluid transport conduits including lumen 113and/or lumen 160. Thermal priming may be accomplished by deliveringfluid at an elevated temperature while preventing the pressure inballoon 120 from exceeding a threshold, such as a threshold which wouldcause expansion of balloon 120 (i.e. prior to initiation of a thermaldose such as while preventing balloon 120 from contacting tissue).Delivery of fluid below this threshold pressure accommodates thermalpriming because it permits the circulation of hot fluid through lumen113 and/or lumen 160, and through balloon 120 itself, prior to inflationof balloon 120, as is shown in FIG. 6A. This pre-heated condition ofballoon 120, as well as lumens 113 and/or 160, ensures a fast thermalrise-time when the balloon is eventually inflated, due to theminimization of heat loss to these components. As a consequence ofthermal priming, the inflation fluid will enter balloon 120 at or nearthe intended temperature for initial treatment, as balloon 120 reachesan inflated state shown in FIG. 6C. FIG. 6D illustrates a magnified viewof the distal portion of device 100 of FIG. 6C.

In one embodiment, a pressure threshold for inflation is achieved byballoon 120's materials of construction, as well as thickness and otherchosen geometric parameters. For example, balloon 120 can be designed tohave a force-stretch diagram similar to the one shown in FIG. 7.Suitable balloon materials include but are not limited to: siliconerubber; latex; neoprene; polyurethane; polyester; and combinations ofthese. In some embodiments, one or more balloon's 120 comprisespolyethylene terephthalate (PET). For a given material, balloon 120 wallthicknesses are selected to be thick enough to substantially resistinflation at or below a pressure threshold. Alternatively oradditionally, one or more ribs may be included on or within balloon 120,not shown but comprising balloon material or other material andconfigured to resist expansion of balloon 120. The pre-inflation shapeof balloon 120 comprises a reduced diameter shape such as to remainseparated or otherwise thermally disengaged from the target tissue. Forexample, a balloon 120 exhibiting a pressure threshold for inflation maybe designed to have a substantially cylindrical shape and composed ofsilicone rubber with 3 mm inside diameter and 1 mm wall thickness. Sucha balloon 120 will resist inflation until a pressure threshold isreached. Below the pressure threshold, balloon 120's diameter and wallthickness will remain substantially unchanged, even as hot fluid flowsthrough balloon 120. If such a balloon 120 is situated inside tubulartarget tissue with an inside diameter of 10 mm, for example, then heattransfer to the target tissue is minimized because balloon 120 remainsphysically disengaged from the target tissue and because the thick wallof balloon 120 and the space between balloon 120 and the target tissuebehaves as a thermal insulator. As the balloon 120 pressure is increasedbeyond the pressure threshold for inflation, balloon 120 diameterincreases to establish uniform and positive contact between balloon 120and the target tissue. Simultaneous with expansion, the wall of balloon120 becomes thinner. Both of these conditions initiate and/or otherwiseimprove heat transfer to the target tissue.

As shown in FIG. 6C, expandable cage 118 is expanded and balloon 120 isin an inflated state. Once the pressure threshold is exceeded andballoon 120 is inflated, higher fluid flow rates may be sustainedwithout over-inflating balloon 120. As has been noted above in referenceto FIGS. 4A and 4B, higher flow rates result in fast thermal-responsetime and greater precision in temperature control. Higher fluid flowrates may be sustained since the inflow pressure to balloon 120 for agiven inflation diameter is increased by the amount of the pressurethreshold, thus increasing the differential pressure across balloon 120.

Device 100 typically includes at least one temperature sensor 130constructed and arranged to measure hot fluid and/or balloon 120temperature at any time before, during, or after the target tissuetreatment. Device 100 may include numerous other types of sensors, asare described in reference to FIG. 1 hereabove. Device 100 may be partof an ablation system, such as an ablation system including atemperature controlled fluid delivery device as is described inreference to FIG. 19 herebelow.

FIG. 8 illustrates a device for treating tissue, positioned in a bodylumen and including an element to prevent luminal collapse, inaccordance with the present inventive concepts. FIG. 8A illustrates across-sectional view of the device of FIG. 8. Device 100 is of similarconstruction, and includes components similar to device 100 of FIGS. 4Aand 4B. In the embodiment illustrated in FIGS. 8A and 8B, thermalpriming is accomplished by sustaining a flow through balloon 120 whileport 163 is held at negative internal pressure relative to the pressureof a heated fluid, entering lumen 160 via port 161. In this embodiment,balloon 120 is structured so as to permit flow of hot fluid throughballoon 120 when it is in its deflated state, as described in referenceto FIGS. 6A and 6B hereabove. As is shown in FIG. 8A, balloon 120 mayinclude one or more support structures, such as flutes 168, which may beconstructed and arranged to prevent collapse of balloon 120 and/or lumen160, such as during a period in which balloon 120 and/or lumen 160 is ata low or negative pressure. Alternative or in addition to flutes 168,other support elements may be included such as a support elementselected from the group consisting of: a helical coil; a strut; a wire;a wire-form structure; a tube; a foam member; a spring; and combinationsof these.

Device 100 typically includes at least one temperature sensor, such assensor 130 described herein, constructed and arranged to measure hotfluid and/or balloon 120 temperature at any time before, during, orafter the target tissue treatment. Device 100 may include numerous othertypes of sensors, as are described in reference to FIG. 1 hereabove.Device 100 may be part of an ablation system, such as an ablation systemincluding a temperature controlled fluid delivery device as is describedin reference to FIG. 19 herebelow.

FIG. 9 illustrates a device for treating tissue, positioned in a bodylumen and including an element to prevent luminal collapse, inaccordance with the present inventive concepts. FIG. 9A illustrates across-sectional view of the device of FIG. 9. Device 100 is of similarconstruction, and includes components similar to device 100 of FIGS. 8and 8A. Device 100 of FIGS. 9 and 9A includes structures that can bepositioned within balloon 120 to provide means for flow despite thecollapse of the balloon under low or negative pressures. Device 100includes rib 121, which comprises an internal support structure embeddedinto the wall of balloon 120. Alternative or in additional to rib 121, asupport element embedded in the wall of balloon 120 may comprise one ormore support elements selected from the group consisting of: ridges;bumps; wire members; increased density portions; modified textureportions; and combinations of these. Ribs 121 and/or other supportmembers may be constructed and arranged to maintain a flow of fluid intoballoon 120 while balloon 120 is deflated or otherwise under low ornegative pressure.

Device 100 typically includes at least one temperature sensor, such assensor 130 described herein, constructed and arranged to measure hotfluid and/or balloon 120 temperature at any time before, during, orafter the target tissue treatment. Device 100 may include numerous othertypes of sensors, as are described in reference to FIG. 1 hereabove.Device 100 may be part of an ablation system, such as an ablation systemincluding a temperature controlled fluid delivery device as is describedin reference to FIG. 19 herebelow.

FIGS. 10A and 10B illustrate a device for treating tissue, positioned ina body lumen and including an expandable element, shown in deflated andinflated states, respectively, in accordance with the present inventiveconcepts. Device 100 is of similar construction, and includes componentssimilar to device 100 of FIGS. 4A and 4B. In the embodiment illustratedin FIGS. 10A and 10B, shaft 164 can be translated forward and backwithin shaft 110. In the illustrated embodiment, thermal priming isaccomplished by selectively and controllably routing a re-circulatingflow of hot fluid so that it bypasses balloon 120. In this embodiment,thermal priming involves repositioning distal end 166 of shaft 164 froma position within balloon 120 to a position proximal to balloon 120, ata time prior to inflation of balloon 120. Priming fluid (e.g. fluid atan elevated temperature) is delivered via port 163 and/or 164, andremoved via port 164 and/or 163 respectively, as is described hereabove.

As shown in FIG. 10B, at the completion of thermal priming, distal end166 of shaft 164 is returned to a position within balloon 120 so thatthe existing pressure differential between inflow and outflow or a newlyselected pressure differential (e.g. an increased pressure differential)results in the rapid inflation of balloon 120.

Device 100 typically includes at least one temperature sensor 130constructed and arranged to measure hot fluid and/or balloon 120temperature at any time before, during, or after the target tissuetreatment. Device 100 may include numerous other types of sensors, asare described in reference to FIG. 1 hereabove. Device 100 may be partof an ablation system, such as an ablation system including atemperature controlled fluid delivery device as is described inreference to FIG. 19 herebelow.

FIGS. 11A and 11B illustrate a device for treating tissue, positioned ina body lumen and including an expandable element, shown in deflated andinflated states, respectively, in accordance with the present inventiveconcepts. Device 100 is of similar construction, and includes componentssimilar to device 100 of FIGS. 4A and 4B. In the embodiment illustratedin FIGS. 11A and 11B, shaft 164 includes a valve 167 positioned alongits length and in fluid communication with lumen 160. Valve 167typically comprises a flap-valve or other one-way valve construction.Valve 167 is oriented such that when negative pressure is applied tolumen 160, such as via suction applied to port 161, valve 167 opens andballoon 120 deflates. With the valve open, fluid introduced throughlumen 113, such as via port 163, bypasses balloon 120, preventing itsinflation, and travels proximally through lumen 160, as shown in FIG.11A. In this configuration, thermal priming can be accomplished bydelivering hot fluid through lumen 113. When a positive pressure isintroduced into lumen 160, such as a positive pressure approximating apressure applied to lumen 113, valve 167 is closed, allowing fluidintroduced through port 163 to inflate balloon 120, as is shown in FIG.11B. Valve 167 may comprise two or more valves, such as valves deployedin similar or dissimilar orientations, such as when fluid administeredin a first direction causes thermal priming and fluid administered inthe opposite direction causes expansion of balloon 120. In analternative embodiment, valve 167 comprises a small diameter conduitbetween lumen 113 and lumen 160, such that thermal priming can beachieved if fluid is delivered at a rate below a threshold. When thethreshold is exceeded, valve 167 provides sufficient resistance suchthat balloon 120 is expanded, such as an expansion to contact and treattarget tissue.

Device 100 typically includes at least one temperature sensor 130constructed and arranged to measure hot fluid and/or balloon 120temperature at any time before, during, or after the target tissuetreatment. Device 100 may include numerous other types of sensors, asare described in reference to FIG. 1 hereabove. Device 100 may be partof an ablation system, such as an ablation system including atemperature controlled fluid delivery device as is described inreference to FIG. 19 herebelow.

FIGS. 12A, 12B and 12C illustrate a device for treating tissue,positioned in a body lumen and including an expandable element, shown inan inflated, a partially inflated, and fully deflated states,respectively, in accordance with the present inventive concepts. Device100 is of similar construction, and includes components similar todevice 100 of FIGS. 4A and 4B. In the embodiment illustrated in FIGS.12A and 12B, device 100 includes a multi-chamber balloon 180, comprisingtwo or more separately inflatable chambers, outer chamber 181 and innerchamber 182. Chambers 181 and 182 are separated by a partition,typically made of material similar to material making up balloon 180.Chambers 181 and 182 may comprise one or more balloon materialsdescribed hereabove, such as elastic and inelastic materials, such as tocreate balloon structures that are compliant and/or non-compliant, orthat expand after being pressurized above a pressure threshold (e.g. thepressure-thresholded balloons described hereabove). When inner chamber182 is inflated, such as with air, the volume of hot fluid required tofill outer chamber 181 is less than a similarly sized balloon with asingle chamber (i.e. without inner chamber 182). Referring specificallyto FIG. 12A, a fluid (e.g. air) enters port 171, travels through lumen170, and fills inner chamber 182. A similar or dissimilar fluid (e.g.hot water or hot saline) enters port 161, travels through lumen 160, andfills outer chamber 181. To deflate outer chamber 181, flow of fluidthrough lumen 160 is ceased and/or a negative pressure is applied toport 163, as is shown in FIG. 12B. Similarly, to deflate inner chamber182, flow of fluid through lumen 170 is ceased and/or a negativepressure is applied to port 171, as is shown in FIG. 12C.

A reduction in the volume of the hot fluid within balloon 180 may beadvantageous for several reasons including but not limited to: a reducedvolume of re-circulating hot fluid within balloon 180 will have ashorter residence time within balloon 180, and in this dynamic system,residence time directly impacts response-time; a reduced volume ofre-circulating hot fluid within balloon 180 will require a shorterinflation time which translates directly into a faster thermalrise-time; and combinations of these. It will be understood that one ormore of chambers 181 and/or 182 of multi-lumen balloon 180 that are notinflated with a hot fluid may instead be inflated with air or othergases or liquids that are not heated but instead are used for thepurposes of a combination of volume displacement and/or insulation.

In FIG. 12C, the inner chamber 182 has also been deflated, such as byapplying a suction to port 171. The fully deflated configuration of FIG.12C may be used to introduce device 100, such as introduction through anendoscope.

In device 100 of FIGS. 12A-12C, multi-lumen balloon 180 is constructedsuch that the functions of inflation/deflation and heat transfer may beassigned to different chambers of balloon 180. Rapid inflation anddeflation of balloon 180 is effected by means of lumen 170 (in fluidcommunication with inner chamber 182, and lumens 160 and/or 113, each influid communication with outer chamber 181. Lumen 170 may becontrollably inflated and deflated with a gas, such as air, or any fluidwhich has a low viscosity and therefore can be rapidly transferred intoand out of inner chamber 182. Lumens 160 and 113 serve as conduits todeliver a heat source for ablation, such as a hot fluid that preferablyhas a high thermal conductivity and optionally a high heat capacity. Inan alternative embodiment, an expandable assembly such as an expandablebasket or radially expandable arms may be placed within inner chamber182, such as to expand inner chamber 182 with or without the infusion offluid into inner chamber 182.

This device of FIGS. 12A-12C may be advantageous for several reasonsincluding but not limited to: separation of the functions ofinflation/deflation and heat transfer permit the efficient selection offluids for each, such as a fluid with appropriate mechanical properties(e.g. low viscosity) that is selected for the inflation/deflationfunction while a fluid with excellent thermal properties (e.g. highthermal conductivity) may be separately selected for the heat transferfunction; the re-circulating flow of the heat transfer fluid mayoptionally remain uninterrupted during the inflation and deflationperiods thus permitting a continual state of thermal readiness of thesystem between inflation cycles; and combinations of these. In someembodiments, inner chamber 182 may be filled with hot fluid, such as totreat target tissue such as when outer chamber 181 is deflated. In theseembodiments, outer chamber 181 may be expanded to move target tissueaway from inner chamber 182, such as to rapidly stop energy transferbetween hot fluid in chamber 182 and target tissue.

It will be understood that multi-lumen balloon 180 may have more thantwo lumens or cavities, in which case the inflation/deflation functionsand the heat transfer functions may be apportioned between those lumensin a variety of ways. It will also be understood that this embodimentmay be implemented in conjunction with any of the additional embodimentsdisclosed herein, so that, for example, the heat transfer portion ofthis embodiment may involve a hot-fluid bolus rather than are-circulating fluid, or a combination of bolus and re-circulating heattransfer may be delivered through multiple lumens in fluid communicationwith the multiple chambers.

Device 100 typically includes at least one temperature sensor 130constructed and arranged to measure hot fluid and/or balloon 120temperature at any time before, during, or after the target tissuetreatment. Device 100 may include numerous other types of sensors, asare described in reference to FIG. 1 hereabove. Device 100 may be partof an ablation system, such as an ablation system including atemperature controlled fluid delivery device as is described inreference to FIG. 19 herebelow.

FIG. 13 illustrates a device for treating tissue, positioned in a bodylumen and including one or more fluid heating coils, in accordance withthe present inventive concepts. Device 100 is of similar construction,and includes components similar to device 100 of FIGS. 4A and 4B. In theembodiment illustrated in FIG. 13, both fast thermal rise-time and fastthermal response-time are accomplished by having fluid re-circulatingthrough lumens 160 and 113 passing through heater coil 190. Additionallyor alternatively, one or more heat emitters may be situated withinballoon 120 and/or within lumens 160 and/or 113. Coil 190 may becontrollably operated by external means, such as controller 360 and/orEDU 330 described in reference to FIG. 19 herebelow. Alternative heatemitters include but are not limited to: resistance heaters, opticalabsorbers, ultrasound emitters, or any other means of dissipating energyinto the fluid stream. It will be understood that a number of means ofconveying energy to remote locations within shaft 110 may be employed,including but not limited to electrical wires, optical fibers, acousticwaveguides and the like. Device 100 includes fluid transport mechanism800, which is configured both to deliver fluid to balloon 120 via port161 and lumen 160 as well as extract fluid from balloon 120 via port 163and lumen 113, via conduits 192 and 191, respectively. Fluid transportmechanism 800 may include a heat exchanger or other heating element,such as in addition to heater coil 190 or as an alternative. In oneembodiment, fluid transport mechanism 800 comprises a single pumpingassembly. In some embodiments, fluid transport mechanism 800 comprises aperistaltic or other pump configured to continuously deliver and extractfluid with a single rotational drive element. The single rotationaldrive element may comprise one or more of: a rotating impeller; areciprocating volumetric displacement element; one or more rollersconfigured to drive fluid through tubing with peristalsis; andcombinations of these.

Device 100 typically includes at least one temperature sensor 130constructed and arranged to measure hot fluid and/or balloon 120temperature at any time before, during, or after the target tissuetreatment. Device 100 may include numerous other types of sensors, asare described in reference to FIG. 1 hereabove. Device 100 may be partof an ablation system, such as an ablation system including atemperature controlled fluid delivery device as is described inreference to FIG. 19 herebelow.

FIG. 14 illustrates a device for treating tissue, positioned in a bodylumen and including multiple fluid directing nozzles, in accordance withthe present inventive concepts. Device 100 is of similar construction,and includes components similar to device 100 of FIGS. 4A and 4B. In theembodiment illustrated in FIG. 14, uniform temperature within balloon120 and along its surface may be accomplished by means of the dynamicmixing of hot fluid, such as within or proximal to balloon 120. Forexample, at least one nozzle can be situated along lumen 160 eitherwithin or leading to balloon 120. As shown, four nozzles 140 a-d havethe effect of accelerating the fluid as it flows through lumen 160,resulting in a jetting action that serves to agitate the fluid body andso eliminate hotter or cooler zones or “dead zones” within balloon 120.Nozzles 140 a-d may be configured as constrictions, small holes, orports, and may be shaped to achieve a particular mixing profile. In theembodiment shown in FIG. 14, fluid is delivered through port 161 suchthat it enters balloon 120 via nozzles 140 a-d and the distal end oflumen 160. In an alternative embodiment, fluid may be delivered toballoon 120 via lumen 113, and extracted from balloon 120 via lumens 160and nozzles 140 a-d.

Device 100 typically includes at least one temperature sensor 130constructed and arranged to measure hot fluid and/or balloon 120temperature at any time before, during, or after the target tissuetreatment. Device 100 may include numerous other types of sensors, asare described in reference to FIG. 1 hereabove. Device 100 may be partof an ablation system, such as an ablation system including atemperature controlled fluid delivery device as is described inreference to FIG. 19 herebelow.

FIG. 15 illustrates a device for treating tissue, positioned in a bodylumen and including flow directors, in accordance with the presentinventive concepts. Device 100 is of similar construction, and includescomponents similar to device 100 of FIGS. 4A and 4B. In the embodimentillustrated in FIG. 15, uniform temperature within balloon 120 and alongits surface may be accomplished by means of mixing a hot fluid as itflows over at least one deflector. For example, fins 141 a and 141 b canbe strategically placed within balloon 120 and/or lumens 160 and/or 113leading to balloon 120 to achieve the mixing of a hot fluid enteringport 161. In the embodiment shown in FIG. 15, fluid is delivered throughport 161 such that it enters balloon 120 via the distal end of lumen160. In an alternative embodiment, fluid may be delivered to balloon 120via lumen 113, and extracted from balloon 120 via lumens 160.

Device 100 typically includes at least one temperature sensor 130constructed and arranged to measure hot fluid and/or balloon 120temperature at any time before, during, or after the target tissuetreatment. Device 100 may include numerous other types of sensors, asare described in reference to FIG. 1 hereabove. Device 100 may be partof an ablation system, such as an ablation system including atemperature controlled fluid delivery device as is described inreference to FIG. 19 herebelow.

FIG. 16 illustrates a device for treating tissue, positioned in a bodylumen and including a balloon with one or more surface modifications, inaccordance with the present inventive concepts. Device 100 is of similarconstruction, and includes components similar to device 100 of FIGS. 4Aand 4B. In the embodiment illustrated in FIG. 16, rapid and efficientheat transfer through the wall of balloon 120 may be accomplished bymeans of a surface modification of balloon 120. Surface modificationsmay include coating 122, for example, a thin-film metallization coating.Alternatively or additionally, coating 122 may comprise a coatingincluding soft and highly compliant materials, such as hydrogels whichare constructed and arranged to conform to various textures of thetarget tissue. Coating 122 may be configured to possess enhanced thermalconductivity. Alternatively or additionally, a surface modification mayinclude impregnation of the wall of balloon 120 with heat transfercompounds 123, such as metallic powders. Alternatively or additionally,the surface modification may include over-sheathing balloon 120 with oneor more expandable heat transfer elements, such as mesh 124, typically awire mesh or other mesh with rapid heat transfer capabilities. These andother surface modifications may have the effect of increasing theeffective thermal conductivity and heat transfer coefficient of theballoon surface in contact with the target tissue.

Alternatively or additionally, rapid and efficient heat transfer throughthe wall of the balloon may be accomplished by means of surfacetexturing to the outer surface of balloon 120, such as to increasesurface area contact with non-smooth tissue. Certain target tissue,notably intestinal tissue, may possess folds, bumps and finger-likeprojections (villi). In one embodiment, improved engagement withnon-smooth tissue may be accomplished by providing the balloon withprojections, not shown, but projections sized and oriented tointerdigitate with the tissue.

Device 100 typically includes at least one temperature sensor 130constructed and arranged to measure hot fluid and/or balloon 120temperature at any time before, during, or after the target tissuetreatment. Device 100 may include numerous other types of sensors, asare described in reference to FIG. 1 hereabove. Device 100 may be partof an ablation system, such as an ablation system including atemperature controlled fluid delivery device as is described inreference to FIG. 19 herebelow.

FIG. 17 illustrates a device for treating tissue, positioned in a bodylumen and including a permeable balloon, in accordance with the presentinventive concepts. Device 100 is of similar construction, and includescomponents similar to device 100 of FIGS. 4A and 4B. In the embodimentillustrated in FIG. 17, balloon 120 includes at least a portion thatcontains holes, pores or otherwise is permeable, permeable membrane 127.During treatment, a biocompatible hot fluid is secreted through membrane127, contacting the target tissue, thus effecting enhanced heattransfer. The rate of seepage or “weeping” of the fluid is selected tobe of such a rate as to be easily conveyed away or drained by the organor easily suctioned and conveyed away by a conduit that is placed incommunication with the lumen of the target tissue, for example lumen 160and/or lumen 113. The placement and pattern of perforations may bechosen to suit the application geometry and the target tissue. Variousmeans are available for the creation of permeable balloon membranesincluding but not limited to: laser perforation; e-beam perforation;mechanical perforation; foaming fabrication; and combinations of these.In some embodiments, balloon 120 comprises a material that becomesporous when expanded, such as a thin material that becomes porous whenexpanded. Balloon 120 may be fabricated using a salt or other materialthat is soluble in a liquid such as water, such as when balloon 120includes salt particles that are dissolved through exposure to a liquidand create permeability in balloon 120 in the locations previouslyoccupied by the salt particles. Balloon 120 may include a coating, suchas a hydrophilic coating configured to maintain a consistently uniform,wet surface.

Device 100 typically includes at least one temperature sensor 130constructed and arranged to measure hot fluid and/or balloon 120temperature at any time before, during, or after the target tissuetreatment. Device 100 may include numerous other types of sensors, asare described in reference to FIG. 1 hereabove. Device 100 may be partof an ablation system, such as an ablation system including atemperature controlled fluid delivery device as is described inreference to FIG. 19 herebelow.

FIG. 18 illustrates a method of treating target tissue, in accordancewith the present inventive concepts. In STEP 210, target tissue isselected, such as is described in applicant's co-pending application PCTApplication Serial Number PCT/US2012/021739, entitled Devices andMethods for the Treatment of Tissue, filed Jan. 18, 2012, the contentsof which are incorporated herein by reference in its entirety. In atypical embodiment, the target tissue comprises at least a length of theduodenum (e.g. approximately the entire length of the duodenum), atleast a width of the duodenum (e.g. full circumferential width) and atleast a depth of the duodenum (e.g. at least the mucosal layer) isselected, such as to create a target tissue volume.

The distal portion of an ablation device is delivered proximate thetarget tissue site, such as via a lumen of an endoscope when the targettissue comprises a portion of the gastrointestinal tract such as theduodenum. One or more treatment elements of the ablation device arepositioned on or near at least a portion of target tissue, such as whenthe target tissue comprises multiple contiguous portions of tissue to betreated. One or more visualization devices, such as an endoscopiccamera, ultrasound device, or fluoroscope may be used to position thetreatment element.

In STEP 220, an optional step of thermal priming is performed, such as adelivery of fluid performed at a pressure low enough to preventtreatment element expansion or otherwise configured to avoid contactwith the treatment element and target tissue. Prior to the thermalpriming, a negative pressure priming procedure may be performed, such asis described in reference to FIG. 2 hereabove. Negative pressure primingcan be used to remove any liquids or gases from the fluid pathways ofthe system, such as the fluid pathways described hereabove includinglumen 160, lumen 113 and balloon 120 of FIG. 2. During thermal priming,one or more components of the ablation device may be exposed to anelevated temperature, such as fluid at an elevated temperaturecirculated to contact the one or more components, such as to prevent aheat-sinking effect of these components when a thermal dose of hot fluidis introduced into the treatment element to treat target tissue. Duringthe delivery of the thermal priming fluids, a vacuum or other negativepressure may be applied to one or more outflow ports of the system.

In STEP 225, an optional step of cooling tissue is performed. Thiscooling may be accomplished by introducing a fluid into a treatmentelement, using similar or dissimilar means than are used to deliver thefluid providing the thermal dose, such as to introduce a circulatingflow of cooling fluid. Alternatively, the cooling fluid may be deliveredproximate or in direct contact with tissue, such as via a cooledinsufflation or other cooled fluid delivered by an endoscope, theablation device, or a separate device advanced proximate the targettissue. Typically this cooling fluid is delivered at or below 43° C.,such as to cool both target and non-target tissue, such as the mucosallayer and the tunica muscularis, respectively. Safety margin tissue,such as the submucosal layer, may also be cooled. These cooling steps,typically performed at temperatures below 37° C. such as at temperaturesbetween 4° C. and 10° C., can be used to prevent non-target tissue frombeing damaged in subsequent hot fluid ablation steps. In someembodiments, cooling below 4° C. may be employed, such as when one ormore cooling fluids are delivered to a treatment element such as aballoon, such as a fluid with a freezing temperature below 0° C. orwater maintained at a temperature just above 0° C. The duration ofapplication of the cooling fluid can be of a fixed time period ordetermined by an algorithm, such as an algorithm based on a measuredtissue parameter such as tissue temperature, tissue type and/or tissuethickness. In some embodiments, an algorithm is used to cool tissueuntil a steady-state condition is reached, such as when the surfacetemperature of tissue remains relatively constant, such as at a constanttemperature between 4° C. and 10° C. Prior to continuing, the coolingfluid may be removed, such as by a negative pressure priming step. Inaddition to protecting non-target tissue, pre-cooling of target tissuemay provide numerous advantages, such as improving the thermal gradientof the treatment. Cooling step 225 may be performed after target tissuetreatment (e.g. after STEP 250), such as to remove residual heat fromtarget and/or non-target tissue. In some embodiments, one or morecooling STEPs 225 are performed for a longer time duration than one ormore target tissue treatment STEPs 230, such as a cooling STEP 225 thatcomprises a time of at least 60 seconds and a treatment STEP 230 thatcomprises a time less than or equal to 60 seconds. Cooling STEP 225 mayinclude application of pressure, such as to reduce perfusion throughtarget tissue. Cooling STEP 225 may include monitoring of temperature,such as to identify real-time temperature levels; maximum or minimumtemperature levels achieved; and/or determine when a steady statetemperature has been achieved.

In STEP 230, treatment of target tissue is performed. In a typicalembodiment, the treatment element is inflated or otherwise expanded,such as when the treatment element is a balloon that is expanded with ahot fluid to treat the target tissue. In a different embodiment, thetreatment element is already in contact with target tissue, such as froman expansion performed in STEPs 220 and/or 225, and hot fluid isintroduced within the treatment element. In yet another embodiment,tubular target tissue may be brought into contact with the treatmentelement by application of a vacuum or other negative pressure on thewalls of the tubular target tissue, such as a vacuum applied through aninsufflation port of an endoscope. Sufficient apposition between thetreatment element and the target tissue can be achieved and/or confirmedthrough pressure regulation (e.g. of hot fluid within the balloon),and/or through adequate results achieved in a leak test such as apressurized leak test or a vacuum leak test. The leak test may comprisedelivery of a fluid such as carbon dioxide proximal to the treatmentelement, with a sensor placed distal to the treatment element, such asthe chemical sensor described in reference to FIG. 19 herebelow.Additionally or alternatively, other leak tests can be used, such as theintroduction of a fluid to achieve a resultant positive pressure withina lumen of target tissue, where monitoring of the decay of the resultantpositive pressure can be used to identify inappropriate apposition ofthe treatment element. Alternatively a vacuum or other negative pressurecan be applied (e.g. as described hereabove to bring tubular targettissue in contact with a treatment element), and the decay in vacuumused to indicate adequacy of apposition of the treatment element.Required pressures and/or balloon inflation diameters may be recordedfor pre-configuration used in further treatment steps. Proper appositionrequirements may be determined prior to delivery of the hot ablativefluid, such as with a body temperature fluid such as air at or near bodytemperature.

Prior to treatment of the target tissue, a tissue layer expansionprocedure may be performed, such as when the target tissue comprisesmucosal tissue of the duodenum and a submucosal tissue injection isperformed. In one embodiment, a submucosal injection procedure isperformed as is described in applicant's co-pending application PCTApplication Serial Number PCT/US2012/021739, entitled Devices andMethods for the Treatment of Tissue, filed Jan. 18, 2012, the contentsof which are incorporated herein by reference in its entirety.Initiation of ablation steps may be performed soon after completion of atissue layer expansion, such as within 15 minutes of a tissue layerexpansion, typically within 10 minutes of tissue layer expansion. Insome embodiments, initiation of ablation steps is performed within 5minutes of tissue layer expansion.

Ablation of the target tissue performed in STEP 230 may be performedusing the rapid rise time and rapid response systems, devices andmethods described hereabove. In a typical embodiment, thermal rise-timeis rapid, such as a thermal rise time in which fluid temperature withinthe treatment element reaches 90% of a target temperature within 5seconds of initiating the treatment element inflation. In anothertypical embodiment, thermal response time is rapid, such as a thermalresponse time in which fluid temperature in the treatment elementreaches 90% of a modified target temperature within 15 seconds ofinitiating the process to modify the delivery element fluid to the newtarget temperature.

In STEP 240, the tissue treatment is monitored, such as by monitoringsignals from one or more sensors, typically one or more temperaturesensors and/or one or more sensors as are described in reference to FIG.19 herebelow. Treatment STEP 230 and monitoring STEP 240 are continuedsimultaneously and/or cyclically sequentially until it is determinedthat adequate treatment has been performed. During the cycling betweenSTEPS 230 and 240, one or more additional steps may be performed such assteps selected from the group consisting of: negative pressure priming;tissue cooling; treatment element repositioning; treatment elementapposition confirmation; target tissue radial expansion such as throughinsufflation; target tissue radial compression such as through theapplication of a negative pressure to the target tissue through anendoscope; and combinations of these. In some embodiments, rapiddelivery of heating fluids followed by cooling fluids are performed toprovide a thermal energy transfer with sufficient control to preciselyablate target tissue while avoiding damage to non-target tissue.

STEP 250 follows in which treatment of target tissue is stopped. In oneembodiment, the expandable treatment element is deflated or otherwisecompacted, such as to remove the treatment element from the targettissue site and the body, or to move the treatment element to adifferent portion of target tissue to be treated. In a differentembodiment, the fluid in the treatment element is brought to atemperature sufficient to stop treatment, such as a temperature at or atleast 10° C. below a target treatment temperature or a temperature below43° C., such as when the treatment element had previously been filledwith fluid at an elevated, ablative temperature. In order to stop targettissue treatment, the fluid in the treatment element may receive acooling fluid, such as a fluid delivered through an inflow port while avacuum or other negative pressure is applied to one or more outflowports. In yet another embodiment, tubular target tissue may be movedaway from the treatment element, such as through the introduction of afluid at a positive pressure, such as the introduction of a gas such asCO₂ applied through an insufflation port of an endoscope. In yet anotherembodiment, the treatment element is translated (e.g. advanced distallyor retracted proximally) from a first target tissue portion to a secondtarget tissue portion, without deflation or otherwise losing appositionwith tissue. This translation is performed such that treatment of thefirst target tissue portion is completed and treatment of the secondtarget tissue portion is initiated, noting that the first target tissueportion and the second target tissue portion may include overlap.

STEPS 210 through 250 are typically repeated a number of times, such asto treat multiple contiguous subportions of target tissue, such asmultiple contiguous portions of duodenal tissue. Each target tissueportion may be unique, or there may be overlap from segment to segment.A formulated approach to quantity of tissue overlap may be used, such asan overlap of approximately 5 mm to 10 mm of one or more dimensions oftarget tissue (e.g. length or width). Alternatively, overlap maycomprise advancing and/or withdrawing the treatment element (e.g. aballoon) by a distance equal to one-half to three-quarters of itslength, for each hot fluid energy delivery. Overlap amounts may vary,such as due to variances in the anatomy. In some embodiments, treatmentof luminal tissue such as duodenal tissue comprises different overlapamounts in one or more angulated or otherwise non-linear portions, suchas overlaps that are greater on an inside curve than an outside curve ina bend portion. Overlap amounts are typically chosen to avoidnon-treated portions of target tissue. Overlapping advancements may beperformed manually by an operator. Alternatively, the system and/orablation device of the present inventive concepts may comprises anautomated advancement or retraction positioning system to ensure apredetermined length of overlap from one tissue treated tissue portionto another, such as the positioning system described in reference toFIG. 19 herebelow. Alternatively or additionally, amount of overlap maybe determined through visual and/or sensorial cues, such as a cuegenerated from: visual image provided by an endoscopic camera; impedancemeasurement performed by an ablation device electrode; and combinationsof these. In one embodiment, a scan or other diagnostic test to confirmcontiguous ablation of target tissue is performed, such as after STEP250, after which identified untreated segments of target tissue aresubsequently treated. A first portion of target tissue treatment may befollowed by a second portion of target tissue treatment after a timedelay, such as a delay sufficient to allow the first target tissueportion to cool. A chosen time may be selected such as to allow thefirst target tissue to cool to a temperature less than 43° C., such as atemperature within 2° C. of a baseline temperature such as bodytemperature. Alternatively or additionally, a cooling procedure may beperformed between treatment of the first portion of target tissue andthe second portion of target tissue.

In STEP 240, the progress of thermal ablation may be monitored bymeasuring and interpreting the residual heat present in the targettissue during the time interval between heat application cycles. Thisinformation may be used to fine-tune or optimize the ablative treatmentof the target tissue. Residual heat is herein defined as an elevation oftissue temperature above normal body temperature at the completion of aheat application. Residual heat is expected to be a measure of theprogress of thermal ablation as it represents that portion of the heatload that has not been dissipated by the target tissue. The presence ofresidual heat may not necessarily indicate that ablation has occurred,but may instead indicate that ablation is being approached. Targettissue that has been damaged or necrosed would be expected to exhibitincreased residual heat, such as due to the complete or partialshut-down of blood perfusion. Therefore, the magnitude of residual heatis expected to be a useful indication of the progress toward and theeventual completion of ablation. The magnitude of residual heat may alsobe influenced by the physiological effect described hereabove, namely,increased blood perfusion due to the application of heat to soft tissue.This effect may be manifested in the early stages of ablation andtherefore may be a useful indicator of the progress towards ablation.

Residual heat may be measured by means of one or more miniaturetemperature sensors located within the cavity of the balloon or othertreatment element, or on its surface. Experiments have confirmed thatresidual heat passes readily into a deflated balloon, provided that theballoon remains within the treatment zone. Alternatively, the balloonmay be inflated with air or any other gas or liquid between treatmentcycles, for the purpose of establishing direct contact with the targettissue for the measurement of residual heat.

Prior to and/or during the treatment applied in STEP 230, a combinationof treatment element (e.g. balloon) compliance and internal pressure maybe used to smooth tissue folds, distend tissue, accommodate variationsin tissue structure and geometry, and/or generally establish uniformcircumferential contact between the balloon and the target tissue.

Prior to and/or during the treatment applied in STEP 230, the treatmentelement may be translated and/or spun, permitting control of thermalcontact time as well as, optionally, a combination of thermal andmechanical action on the target tissue. The adjustment of thermalcontact time by way of treatment element motion is to be understood as ameans of adjusting thermal dose during treatment.

The treatment applied in STEP 230 may comprise treatment with a hotfluid balloon as well as other treatment means, which may also reside onthe same catheter or delivery device as the hot balloon or,alternatively, be deployed on a separate device.

In some embodiments, a fluid may be introduced at the beginning of atreatment that is different than fluid delivered at a later time.Alternatively or additionally, an initial target temperature of athermal dose may be higher than a subsequent, modified targettemperature. The effect of these higher initial temperatures will causethe target tissue temperature to rise faster than if a lower initialtemperature fluid or target temperature is used. Prior to the targettissue reaching a level equating to these initial fluid and/or targettemperatures, a lower fluid and/or target temperature is used. Thisconfiguration increases the thermal rise of target tissue temperature,while avoiding longer term exposure of tissue to these highertemperatures, such as to reduce damage to non-target tissue.

Negative pressure priming, such as the negative pressure primingdescribed hereabove as an optional portion of STEP 220, can be performedafter one or more previous tissue treatments have been performed, suchas to remove one or more fluids that would otherwise cool a fluiddelivered as a thermal dose, thus improving the rise time of the thermaldose.

Tissue cooling, such as the tissue cooling performed in STEP 225, can beperformed after one or more previous tissue treatments have beenperformed, such as to remove thermal energy from tissue. The removal ofthis thermal energy can be used to precisely ablate certain layers oftissue while leaving deeper layers undamaged, such as to prevent damageto non-target tissue while fully ablating target tissue. The duration ofapplication of the cooling fluid can be of a fixed time period ordetermined by an algorithm, such as an algorithm based on a measuredtissue parameter such as tissue temperature, tissue type and/or tissuethickness. Tissue cooling may be used when overlapping target tissuesegments are treated, such as when non-target tissue proximate a tissuesegment has been elevated to a temperature approaching 43° C. Tissuecooling may be delivered to bring the non-target tissue to approximately37° C. such as during a cooling procedure including a balloon filledwith fluid at approximately 37° C. Alternatively, tissue tooling may bedelivered to bring the non-target tissue to a level lower than 37° C.,such as during a cooling procedure including a balloon filled with fluidbetween 4° C. and 10° C.

Referring now to FIG. 19, a system for ablating or otherwise treatingtarget tissue is illustrated, consistent with the present inventiveconcepts. System 300 is constructed and arranged to treat target tissue10, including one or more tissue portions. System 300 may include one ormore ablation devices, such as those described hereabove. In theembodiment of FIG. 19, system 300 includes a multiple filament elongatedevice 301 comprising shafts 311 a and 311 b. In some embodiments,device 301 comprises a flexible portion with a diameter less than 6 mmand a length of 100 cm or longer. Shaft 311 a has a distal end 312.Shafts 311 a and 311 b are sized and configured such that shaft 311 a isslidingly received by shaft 311 b. Shafts 311 a and 311 b have beeninserted through a working channel (e.g. a 6 mm working channel), lumen351, of endoscope 350. Shafts 311 a and 311 b may be inserted over aguidewire, such as guidewire 371 shown exiting distal end 312. Device301 further includes two expandable tissue treatment elements,expandable treatment element 322 a, and expandable treatment element 322b, mounted to shafts 311 a and 311 b, respectively. Treatment elements322 a and 322 b may be configured in various forms to treat the targettissue, such as in one or more of the treatment element forms describedin applicant's co-pending application PCT Application Serial NumberPCT/US2012/021739, entitled Devices and Methods for the Treatment ofTissue, filed Jan. 18, 2012, the contents of which are incorporatedherein by reference in its entirety. In one embodiment, elements 322 aand 322 b comprise expandable balloons, such as one or more of: acompliant balloon; a non-compliant balloon; a balloon with a pressurethreshold; a balloon with compliant and non-compliant portions; aballoon with a fluid entry port; a balloon with a fluid exit port; andcombinations of these. In another embodiment, treatment element 322 acomprises an abrasive element configured for abrading tissue; andtreatment element 322 b comprises an energy delivery element such as anenergy delivery element configured to deliver RF energy. Shafts 311 aand 311 b may include one or more lumens passing therethrough, and maycomprise wires or optical fibers for transfer of data and/or energy.Expandable treatment element 322 b typically comprises a treatmentelement constructed and arranged such as balloons 120 referred to inFIGS. 1 through 17 hereabove. Shaft 311 b may comprise one or moreshafts, such as one or more concentric shafts configured to deliveryand/or recirculated hot fluid through treatment delivery element 322 b,such as to deliver a bolus of hot fluid energy or other thermal dose ofthe present inventive concepts. Device 301 may comprise a singletreatment element 322 b without inclusion of treatment element 322 a andits associated components, similar to devices 100 described in referenceto FIGS. 1 through 17 hereabove.

Endoscope 350 may be a standard endoscope, such as a standardgastrointestinal endoscope, or a customized endoscope, such as anendoscope including sensor 353 configured to provide information relatedto the tissue treatment of the present inventive concepts. Sensor 353and the other sensors of system 300 may be a sensor selected from thegroup consisting of: heat sensors such as thermocouples; impedancesensors such as tissue impedance sensors; pressure sensors; bloodsensors; optical sensors such as light sensors; sound sensors such asultrasound sensors; electromagnetic sensors such as electromagneticfield sensors; and combinations of these. Sensor 353 may be configuredto provide information to one or more components of system 300, such asto monitor the treatment of target tissue 10 and/or to treat targettissue 10 in a closed loop fashion. Energy delivery may be modified byone or more sensor readings. In one embodiment, an algorithm processesone or more sensor signals to modify amount of energy delivered, powerof energy delivered and/or temperature of energy delivery.

A sensor such as a chemical detection sensor may be included, such as toconfirm proper apposition of treatment elements 322 a and/or 322 b. Inthis configuration, a chemical sensor such as a carbon dioxide sensorcan be placed distal to treatment element 322 a and/or 322 b, and afluid such as carbon dioxide gas is introduced proximal to the treatmentelement 322 a and/or 322 b. Detection of the introduced fluid mayindicate inadequate apposition of treatment element 322 a and/or 322 b,such as to prevent inadequate transfer of energy to the target tissue.

Endoscope 350 may include camera 352, such as a visible light,ultrasound and/or other visualization device used by the operator ofsystem 300 prior to, during or after the treatment of target tissue 10,such as during insertion or removal of endoscope 350 and/or shafts 311 aand 311 b. Camera 352 may provide direct visualization of internal bodyspaces and tissue, such as the internal organs of the gastrointestinaltract. Endoscope 350 may be coupled with or otherwise include aguidewire, such as to allow insertion of endoscope 350 into the jejunum.

System 300 may be configured to perform insufflation of the body lumen.The body lumen may be pressurized, such as by using one or more standardinsufflation techniques and/or a technique as described in reference toFIGS. 8A and 8B hereabove, for example. Insufflation fluid may beintroduced through lumen 354 of endoscope 350. Lumen 354 travelsproximally and connects to a source of insufflation liquid or gas, notshown, but typically a source of air, CO₂ and/or water. Alternatively oradditionally, insufflation fluid may be delivered by device 301, such asthrough shaft 311 a and/or 311 b, or through a port in treatment element322 a and/or 322 b, ports not shown but fluidly attached to a source ofinsufflation liquid or gas, also not shown. Alternatively oradditionally, a separate device, configured to be inserted throughendoscope 350 or to be positioned alongside endoscope 350, may have oneor more lumens configured to deliver the insufflation fluid. System 300may include one or more occlusive elements or devices, such asexpandable treatment element 322 a or another expandable device, notshown but configured to radially expand such as to fully or partiallyocclude the body lumen, such that insufflation pressure can be achievedand/or maintained over time (e.g. reduce or prevent undesired migrationof insufflation fluid). The one or more occlusive elements or devicesmay be positioned proximal to and/or distal to the luminal segment to beinsufflated.

The treatment elements of the present inventive concepts, such astreatment elements 322 a and/or 322 b of FIG. 19, may have a fixeddiameter or they may be expandable. Expandable elements may compriseinflatable balloons, expandable cages, radially deployable arms, and thelike. Treatment elements may include an energy delivery element orarrays of elements, such as an array of balloon lobes for delivery ofthermal energy from a hot fluid. Energy delivery elements may beconfigured to deliver one or more different forms of energy. Energy maybe delivered in constant or varied magnitudes or other energy levels.Energy may be continuous or pulsed, and may be delivered in aclosed-loop fashion. Energy delivery may be varied from a first tissuelocation to a second location, such as a decrease in energy from a firsttreated location to a second treated location when the second treatedlocation is thinner than the first treated location. Alternatively oradditionally, energy delivery may be varied during a single applicationto a single tissue location, such as by adjusting the amount of energydelivered, or by moving a portion of the energy delivery element, suchas by deflating an energy delivery element as has been described indetail hereabove.

Treatment elements 322 a and/or 322 b may be configured to cause thecomplete or partial destruction of the target tissue, such as thecomplete or partial destruction of the duodenal mucosa. Treatmentelements 322 a and/or 322 b may be configured to remove previouslytreated and/or untreated tissue. Pressure maintained within treatmentelements 322 a and/or 322 b can be set and/or varied to adjust thetreatment being performed such as to: adjust the depth of treatment;adjust the force applied by a mechanical abrasion device; adjust theamount of energy applied during thermal energy delivery (e.g. bychanging tissue contact); and combinations of these.

Treatment elements 322 a and 322 b may include sensors 316 a and 316 b,respectively. Sensors 316 a and 316 b may each be one or more sensors asdescribed hereabove. Sensor 316 a may be a sensor configured to provideinformation related to the tissue treatment performed by treatmentelement 322 a, such as a visualization sensor mounted to treatmentelement 322 a that is configured to differentiate tissue types that areproximate treatment element 322 a, such as to differentiate mucosal andsubmucosal tissue. Sensor 316 b may be a sensor configured to provideinformation related to the tissue treatment performed by treatmentelement 322 b, such as a temperature sensor mounted to treatment element322 b and configured to monitor the temperature of treatment element 322b and/or tissue proximate treatment element 322 b.

Energy Delivery and Fluid Transport Unit (EDU) 330 may be configured todeliver and extract one or more fluids from treatment element 322 aand/or 322 b, as well as deliver one or more forms of energy to targettissue. In one embodiment, EDU 330 is configured to deliver one or moresupplies of hot fluid, such as hot water or saline to a balloontreatment element. In these embodiments, EDU 330 typically includes oneor more fluid pumps, such as one or more peristaltic, displacement orother fluid pumps; as well as one or more heat exchangers or other fluidheating elements internal or external to device 301. EDU 330 may beconstructed and arranged to rapidly deliver and/or withdraw fluid toand/or from treatment elements 322 a and/or 322 b with one or more fluidtransport means. Fluid transport means may include a pump configured todeliver fluid at a flow rate of at least 50 ml/min and/or a pump orvacuum source configured to remove fluid at a flow rate of at least 50ml/min. A pump or vacuum source may be configured to continuouslyexchange hot fluid and/or to perform a negative pressure priming eventto remove fluid from one or more fluid pathways of device 301. EDU 330and/or device 301 may include one or more valves in the fluid deliveryand/or fluid withdrawal pathways, such as the valves described inreference to FIG. 11A-B hereabove or one or more other valves in thefluid pathway with treatment element 322 a and/or 322 b. Valves may beconfigured to control entry of fluid into an area and/or to maintainpressure of fluid within an area. Valves may be used to transition froma heating fluid, such as a fluid of 90° C. maintained in a treatmentelement for approximately 12 seconds, to a cooling fluid, such as afluid between 4° C. and 10° C. maintained in the treatment element forapproximately 30 to 60 seconds. Typical valves include but are notlimited to: duck-bill valves; slit valves; electronically activatedvalves; pressure relief valves; and combinations of these. EDU 330 maybe configured to rapidly inflate and/or deflate treatment elements 322 aand/or 322 b, such as has been described hereabove. EDU 330 may beconfigured to purge the fluid pathways of device 301 with a gas such asair, such as to remove cold or hold fluid from device 301 and/or toremove gas bubbles from device 301.

In another embodiment, EDU 330 is configured to deliver at leastradiofrequency (RF) energy, and system 300 includes ground pad 332configured to be attached to the patient (e.g. on the back of thepatient), such that RF energy can be delivered in monopolar deliverymode. Alternatively or additionally, EDU 330 may be configured todeliver energy in a bipolar RF mode, such as when treatment element 322b is configured to deliver RF energy and/or system 300 includes a secondenergy delivery element, not shown but typically including one or moreelectrodes or electrically conductive surfaces.

System 300 may include controller 360, which typically includes agraphical user interface, not shown but configured to allow one or moreoperators of system 300 to perform one or more functions such asentering of one or more system input parameters and visualizing and/orrecording of one or more system output parameters. Typical system inputparameters include but are not limited to: temperature of a fluid to bedelivered to a treatment element such as a balloon; temperature of acooling fluid to be delivered; flow rate of a hot fluid to be delivered;volume of a hot fluid to be delivered; type of energy to be deliveredsuch as RF energy, thermal energy and/or mechanical energy; quantity ofenergy to be delivered such as a cumulative number of joules of energyto be delivered or peak amount of energy to be delivered; types andlevels of combinations of energies to be delivered; energy deliveryduration; pulse width modulation percentage of energy delivered; numberof reciprocating motions for an abrasive device to transverse;temperature for a treatment element such as target temperature ormaximum temperature; insufflation pressure; insufflation duration; andcombinations of these. System input parameters may include informationbased on patient anatomy or conditions such as pre-procedural orpen-procedural parameters selected from the group consisting of: mucosaldensity and/or thickness; mucosal “lift” off of submucosa after asubmucosal injection; longitudinal location of target tissue within theGI tract; and combinations of these. Typical system output parametersinclude but are not limited to: temperature information such as tissueand/or treatment element temperature information; pressure informationsuch as balloon pressure information or insufflation pressureinformation; force information such as level of force applied to tissueinformation; patient information such as patient physiologic informationrecorded by one or more sensors; and combinations of these.

Controller 360 and/or one or more other components of system 300 mayinclude an electronics module, such as an electronics module including aprocessor, memory, software, and the like. Controller 360 is typicallyconfigured to allow an operator to initiate, modify and cease treatmentof tissue by the various components of system 300, such as bycontrolling EDU 330. Controller 360 may be configured to adjust thetemperature, flow rate and/or pressure of fluid delivered to expandabletreatment element 322 a and/or 322 b. Controller 360 may be configuredto initiate insufflation and/or to adjust insufflation pressure.Controller 360 may be configured to deliver energy (e.g. from EDU 330)or other tissue treatment in a closed-loop fashion, such as by modifyingone or more tissue treatment parameters based on signals from one ormore sensors of system 300. Controller 360 may be programmable such asto allow an operator to store predetermined system settings for futureuse. System 300, EDU 330 and/or controller 360 may be constructed andarranged to modify the temperature, flow rate and/or pressure of a fluiddelivered to one or more treatment elements based a parameter selectedfrom the group consisting of: one or more measured properties of thedelivered fluid; one or more measured properties of the treatmentelement; one or more measured properties of the target tissue; andcombinations of these.

Controller 360 and EDU 330 may be configured to deliver energy inconstant, varied, continuous and discontinuous energy delivery profiles.Pulse width modulation and/or time division multiplexing (TDM) may beincorporated to achieve precision of energy delivery, such as to ensureablation of target tissue while leaving non-target tissue intact.

System 300 may include a mechanism configured to apply motion totreatment elements 322 a and/or 322 b, such as motion transfer element335. Motion transfer element 335 may be configured to rotate and/oraxially translate shafts 311 a and/or 311 b such that treatment elements322 a and/or 322 b, respectively, are rotated and/or translated. Motiontransfer element 335 may be configured to rotate treatment elements 322a and 322 b independently or in unison. Motion transfer element 335 mayinclude one or more rotational or linear drive assemblies, such as thoseincluding rotational motors, magnetic and other linear actuators, andthe like which are operably connected to shaft 311 a and/or 311 b.Shafts 311 a and/or 311 b are constructed with sufficient columnstrength and/or torque transfer properties to sufficiently rotate and/ortranslate treatment elements 322 a and/or 322 b, respectively, duringassociated tissue treatment. Motion transfer element 335 may be incommunication with controller 360, such as to activate, adjust and/orotherwise control motion transfer element 335 and thus the motion oftreatment element 322 a and/or treatment element 322 b. Motion transferelement 335 may be manually driven and/or automatically (e.g. motor)driven. Alternatively or additionally, motion transfer element 335 maybe used to advance or retract treatment element 322 a and/or 322 b froma first position to treat a first portion of target tissue, to a secondposition to treat a second portion of target tissue. In this embodiment,repositioning of treatment element 322 a and/or 322 b may be configuredto provide overlapping treatment, such as the overlapping treatmentdescribed in reference to FIG. 18 hereabove.

Controller 360 may be configured to control energy delivery, such ascontrolling energy delivery to treatment element 322 a and/or 322 b. Forexample, if treatment element 322 b is an RF electrode array, and energydelivery unit 330 comprises an RF generator, controller 360 may beprogrammed to provide a specific amount of RF energy for a definedperiod of time. In another example, if treatment element 322 b is aheated saline balloon, then controller 360 can be configured to provideand withdraw heated saline to treatment element 322 b, such as throughan energy transfer tube not shown, at a desired temperature and for adesired time period. Controller 360 may be configured for manualcontrol, so that the operator first initiates the energy delivery, thenallows the treatment element 322 b to ablate the tissue for some timeperiod, after which the operator terminates the energy delivery.

System 300 may further include one or more imaging devices, such asimaging device 370. Imaging device 370 may be configured to be insertedinto the patient and may comprise a visual light camera; an ultrasoundimager; an optical coherence domain reflectometry (OCDR) imager; and/oran optical coherence tomography (OCT) imager, such as when integral to,attached to, contained within and/or proximate to shaft 311 a and/or 311b. Imaging device 370 may be inserted through a separate working channelof endoscope 350, lumen not shown. In one embodiment, imaging device 370is an ultrasound transducer connected to a shaft, not shown butsurrounded by shaft 311 a and typically rotated and/or translated tocreate a multi-dimensional image of the area surrounding imaging device370. Alternatively or additionally, imaging device 370 may be externalto the patient, such as an imaging device selected from the groupconsisting of: an X-ray; a fluoroscope; an ultrasound image; an MRI; aPET Scanner; and combinations of these.

System 300 may further include protective cap 380, configured to bepositioned proximate tissue to prevent damage to certain tissue duringenergy delivery or other tissue treatment event. Protective cap 380 maybe delivered with endoscope 350 or another elongate device such that cap380 can be placed over and then positioned to protect the Ampulla ofVater. In a typical embodiment, protective cap 380 is removed within 24hours of placement, such as by being removed during the procedure aftertreatment of the target tissue.

System 300 may further include a tissue expanding device 390, configuredto expand the target tissue area, such as sub-mucosal tissue expandingdevice. Tissue expansion can greatly alleviate the need for precision oftreatment, such as precision of energy delivery, due to the increasedsize (e.g. increased depth) of the target and an associated safety zoneof tissue to which treatment causes no significant adverse event (e.g.an expanded submucosal layer prior to a mucosal layer ablation).

System 300 may further include one or more pharmaceutical or otheragents 500, such as an agent configured for systemic and/or localdelivery to a patient. These agents may be delivered, pre-procedurally,peri-procedurally and/or post-procedurally. The agents may be configuredto improve healing, such as agents selected from the group consistingof: antibiotics, steroids, mucosal cytoprotective agents such assucralfate, proton pump inhibitors or other acid blocking drugs; andcombinations of these. Alternative or in addition to these agents,pre-procedural and/or post-procedural diets may be employed.Pre-procedural diets may include food intake that is low incarbohydrates and/or low in calories. Post-procedural diets may includefood intake that comprise a total liquid diet or a diet that is low incalories and/or low in carbohydrates.

In a typical embodiment, system 300 does not include a chronicallyimplanted component or device, only body inserted devices that areremoved at the end of the clinical procedure or shortly thereafter, suchas devices removed within 8 hours of insertion, within 24 hours ofinsertion and/or within one week of insertion. In an alternativeembodiment, implant 510 may be included. Implant 510 may comprise one ormore of: a stent; a sleeve; and a drug delivery device such as a coatedstent, a coated sleeve and/or an implanted pump.

Each of the components of system 300 may be removably attached toanother component, particularly controller 360, EDU 330, motion transferelement 335, ground pad 332 and endoscope 350 and elongate device 301.

Numerous embodiments of the systems, methods and devices for treatingtarget tissue described hereabove include the delivery of a hot fluid,such as fluid delivered at a temperature above 43° C., typically above60° C., to deliver a thermal dose to at least a portion of the targettissue. One or more cooling fluids may be delivered to limit the thermaldose and/or to rapidly decrease the delivery of heat energy to tissue.In some alternative embodiments, a chilled fluid, such as a fluid below20° C., typically below 0° C. is used to deliver a thermal dose toablate tissue, such as through the incorporation of a cryogenic sourceconfigured to chill fluid delivered to an expandable treatment elementsuch as one or more balloons. In these cryogenic ablation embodiments, awarming fluid may be delivered to limit the thermal dose and/or torapidly decrease an ongoing cryogenic ablation.

While the preferred embodiments of the devices and methods have beendescribed in reference to the environment in which they were developed,they are merely illustrative of the principles of the inventions.Modification or combinations of the above-described assemblies, otherembodiments, configurations, and methods for carrying out the invention,and variations of aspects of the invention that are obvious to those ofskill in the art are intended to be within the scope of the claims. Inaddition, where this application has listed the steps of a method orprocedure in a specific order, it may be possible, or even expedient incertain circumstances, to change the order in which some steps areperformed, and it is intended that the particular steps of the method orprocedure claim set forth herebelow not be construed as beingorder-specific unless such order specificity is expressly stated in theclaim.

What is claimed is:
 1. A system for treating target tissue, the systemcomprising: (1) an ablation device comprising: an elongate tube with aproximal portion, a distal portion, and at least one lumen extendingfrom the proximal portion to the distal portion; and an expandabletreatment element mounted to the elongate tube distal portion and influid communication with the at least one lumen; and (2) an energydelivery unit constructed and arranged to deliver a thermal dose to thetarget tissue by (a) delivering a heated fluid to the expandabletreatment element to ablate the target tissue, (b) applying a negativepressure to remove the heated fluid from the expandable treatmentelement, and (c) subsequently delivering a cooling fluid to theexpandable treatment element to cool the target tissue, wherein thecooling fluid is delivered to the expandable treatment element at atemperature at least 10° C. below the temperature of the heated fluid.2. The system according to claim 1, wherein the energy delivery unit isconfigured to provide emptying cycles by applying the negative pressurebetween heating and cooling cycles.
 3. The system according to claim 1,wherein the heating fluid, the cooling fluid, and the negative pressureare delivered through the at least one lumen in the elongate tube. 4.The system according to claim 1, wherein the at least one lumencomprises a first lumen for the delivery of fluid to the expandabletreatment element, and a second lumen for the removal of fluids from theexpandable treatment element.
 5. The system according to claim 1,wherein the delivery of the heated fluid comprises circulating heatedfluid through the expandable treatment element.
 6. The system accordingto claim 5, wherein the heated fluid is maintained at a relativelyconstant temperature while in the expandable treatment element.
 7. Thesystem according to claim 6, wherein the heated fluid is maintained at atemperature between 65° C. and 99° C.
 8. The system according to claim1, wherein the system is constructed and arranged to deliver multiplethermal doses of energy to the target tissue.
 9. The system according toclaim 8, wherein a first dose is delivered to a first tissue locationand a second dose is delivered to a second tissue location.
 10. Thesystem according to claim 1, further comprising an inflow port and anoutflow port, the inflow port and outflow port in fluid communicationwith the expandable treatment element.
 11. The system according to claim1, wherein the thermal dose is constructed and arranged to ablateduodenal mucosa while avoiding damage to the duodenal serosa.
 12. Thesystem according to claim 1, wherein the system is further constructedand arranged to thermally prime the expandable treatment element. 13.The system according to claim 1, wherein the system is furtherconstructed and arranged to inflate the expandable treatment elementwithin 10 seconds.
 14. The system according to claim 1, wherein theheated fluid and/or the cooling fluid is delivered at a relativelyconstant temperature.
 15. The system according to claim 14, wherein theheated fluid is delivered at a temperature of approximately 65° C. forapproximately 30 seconds to 60 seconds.
 16. The system according toclaim 14, wherein the heated fluid is delivered a temperature ofapproximately 70° C. for approximately 5 seconds to 45 seconds.
 17. Thesystem according to claim 14, wherein the heated fluid is delivered at atemperature of approximately 75° C. for approximately 3 seconds to 40seconds.
 18. The system according to claim 14, wherein the heated fluidis delivered at a temperature of approximately 80° C. for approximately3 seconds to 30 seconds.
 19. The system according to claim 14, whereinthe heated fluid is delivered at a temperature of approximately 90° C.for approximately 3 seconds to 20 seconds.
 20. The system according toclaim 1, wherein the system comprises a thermal response time such thatthe thermal dose temperature reaches 90% of a modified targettemperature within 15 seconds of initiating a change to the modifiedtarget temperature.
 21. The system according to claim 1, wherein thecooling fluid is delivered at a temperature of less than 37° C.
 22. Thesystem according to claim 1, wherein the cooling fluid is delivered at atemperature of less than 10° C.
 23. The system according to claim 1,wherein the cooling fluid is delivered for at least 15 seconds.
 24. Thesystem according to claim 1, wherein the delivering of the cooling fluidis configured to cool the target tissue to a temperature of less than43° C.